G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
G00000961 (Mus musculus)

Databases (9)

Curated Gene
OTTHUMG00000134811 (Vega human gene)
ENSG00000135406 (Ensembl human gene)
5630 (Entrez Gene)
1201 (G2Cdb plasticity & disease)
PRPH (GeneCards)
170710 (OMIM)
Marker Symbol
HGNC:9461 (HGNC)
Protein Expression
2437 (human protein atlas)
Protein Sequence
P41219 (UniProt)

Synonyms (1)

  • PRPH1

Literature (29)

Pubmed - other

  • Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence.

    McLenachan S, Goldshmit Y, Fowler KJ, Voullaire L, Holloway TP, Turnley AM, Ioannou PA and Sarsero JP

    Cell and Gene Therapy Research Group, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia. smclenachan@graffiti.net

    The development of homologous recombination methods for the precise modification of bacterial artificial chromosomes has allowed the introduction of disease causing mutations or fluorescent reporter genes into human loci for functional studies. We have introduced the EGFP gene into the human PRPH-1 locus to create the Peripherin-EGFP (hPRPH1-G) genomic reporter construct. The hPRPH1-G reporter was used to create transgenic mice with an intrinsically fluorescent peripheral nervous system (PNS). During development, hPRPH1-G expression was concomitant with the acquisition of neuronal cell fate and growing axons could be observed in whole embryo mounts. In the adult, sensory neurons were labeled in both the PNS and central nervous system, while motor neurons in the spinal cord had more limited expression. The fusion protein labeled long neuronal processes, highlighting the peripheral circuitry of hPRPH1-G transgenic mice to provide a useful resource for a range of neurobiological applications.

    Transgenic research 2008;17;6;1103-16

  • A comparative immunohistochemical analysis of small round cell tumors of childhood: utility of peripherin and alpha-internexin as markers for neuroblastomas.

    Willoughby V, Sonawala A, Werlang-Perurena A and Donner LR

    Department of Pathology, Scott and White Memorial Hospital, Temple, TX 76508, USA.

    Immunohistochemical study of neuroblastomas, Ewing sarcomas, rhabdomyosarcomas, and Wilms tumors demonstrate specific expression of peripherin and alpha-internexin in 20/22 and 6/22 cases of neuroblastomas, respectively. Microtubule-associated protein 1B (MAP 1B) was strongly and diffusely expressed in all 22 cases of neuroblastomas, but was also focally or multifocally expressed in 9/12 rhabdomyosarcomas and also in the blastema and stroma of 8/11 Wilms tumors. All rhabdomyosarcomas strongly and diffusely express nestin, but this marker was also expressed, multifocally, in 15/22 neuroblastomas and also in the blastema and stroma of all 11 Wilms tumors. NeuN, a neuron-specific nuclear protein, was expressed focally in 1 case of neuroblastoma and diffusely in 2 other cases (3/22). Surprisingly, it was also focally expressed in 2/12 rhabdomyosarcomas. In contrast, all 7 cases of Ewing sarcoma were negative for peripherin, MAP 1B, alpha-internexin, NeuN, and nestin. Thirteen neuroblastomas were also immunostained for neurofilaments, tyrosinase, and anaplastic lymphoma kinase 1 (ALK 1), and were found to be negative for these markers. Our results confirm that peripherin and alpha-internexin are neuroblastoma markers useful for the differential diagnostic work-up of small round cell tumors of childhood. Strong diffuse immunoreactivity for MAP 1B favors a diagnosis of neuroblastoma, whereas strong diffuse immunoreactivity for nestin favors a diagnosis of rhabdomyosarcoma.

    Applied immunohistochemistry & molecular morphology : AIMM 2008;16;4;344-8

  • Protein kinase Cepsilon binds peripherin and induces its aggregation, which is accompanied by apoptosis of neuroblastoma cells.

    Sunesson L, Hellman U and Larsson C

    Center for Molecular Pathology, Lund University, Entrance 78, 3rd floor, Malmö University Hospital, UMAS SE-205 02 Malmö

    A hallmark of the afflicted nervous tissue in amyotrophic lateral sclerosis is the presence of protein aggregates, which to a large extent contain the intermediate filament protein peripherin. Here we show that activation of protein kinase C (PKC) or overexpression of PKCepsilon induces the aggregation of peripherin in cultured neuroblastoma cells with elevated amounts of peripherin. The formation of aggregates was coupled to an increased apoptosis, suggesting a functional link between these events. Both induction of aggregates and apoptosis were suppressed in cells that had been transfected with small interfering RNAs targeting PKCepsilon. PKCepsilon and peripherin associate as shown by co-immunoprecipitation, and the interaction is dependent on and mediated by the C1b domain of PKCepsilon. The interaction was specific for PKCepsilon since corresponding structures from other isoforms did not co-precipitate peripherin, with the exception for PKCeta and -, which pulled down minute amounts. PKCepsilon interacts with vimentin through the same structures but does not induce its aggregation. When the PKCepsilon C1b domain is expressed in neuroblastoma cells together with peripherin, both phorbol ester-induced peripherin aggregation and apoptosis are abolished, supporting a model in which PKCepsilon through its interaction with peripherin facilitates its aggregation and subsequent cell death. These events may be prevented by expressing molecules that bind peripherin at the same site as PKCepsilon.

    The Journal of biological chemistry 2008;283;24;16653-64

  • An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology.

    Xiao S, Tjostheim S, Sanelli T, McLean JR, Horne P, Fan Y, Ravits J, Strong MJ and Robertson J

    Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5S 3H2.

    The neuronal intermediate filament protein peripherin is a component of ubiquitinated inclusions and of axonal spheroids in amyotrophic lateral sclerosis (ALS). Overexpression of peripherin causes motor neuron degeneration in transgenic mice and variations within the peripherin gene have been identified in ALS cases. We have shown previously the abnormal expression of a neurotoxic peripherin splice variant in transgenic mice expressing mutant superoxide dismutase-1. These findings indicated that abnormalities of peripherin splicing may occur in ALS. In the current study, peripherin splice variants were identified by reverse transcription-PCR of human neuronal RNA and comparisons in expression made between control and ALS spinal cord using Western blot analysis and immunocytochemistry. Using this approach we have identified a novel peripherin transcript retaining introns 3 and 4 that results in a 28 kDa splice isoform, designated Per 28. Using an antibody specific to Per 28, we show that this isoform is expressed at low stoichiometric levels from the peripherin gene, however causes peripherin aggregation when its expression is upregulated. Importantly we show an upregulation of Per 28 expression in ALS compared with controls, at both the mRNA and protein levels, and that Per 28 is associated with disease pathology, specifically round inclusions. These findings are the first to establish that peripherin splicing abnormalities occur in ALS, generating aggregation-prone splice isoforms.

    Funded by: NINDS NIH HHS: R21.NS051738

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2008;28;8;1833-40

  • Identification of peripherin as a Akt substrate in neurons.

    Konishi H, Namikawa K, Shikata K, Kobatake Y, Tachibana T and Kiyama H

    Department of Anatomy and Neurobiology, Osaka City University, Graduate School of Medicine, Osaka 545-8585, Japan.

    Activation of Akt-mediated signaling pathways is crucial for survival and regeneration of injured neurons. In this study, we attempted to identify novel Akt substrates by using an antibody that recognized a consensus motif phosphorylated by Akt. PC12 cells that overexpressed constitutively active Akt were used. Using two-dimensional PAGE, we identified protein spots that exhibited increased immunostaining of the antibody. Mass spectrometry revealed several major spots as the neuronal intermediate filament protein, peripherin. Using several peripherin fragments, the phosphorylation site was determined as Ser(66) in its head domain in vitro. Furthermore, a co-immunoprecipitation experiment revealed that Akt interacted with the head domain of peripherin in HEK 293T cells. An antibody against phosphorylated peripherin was raised, and induction of phosphorylated peripherin was observed not only in Akt-activated cultured cells but also in nerve-injured hypoglossal motor neurons. These results suggest that peripherin is a novel substrate for Akt in vivo and that its phosphorylation may play a role in motor nerve regeneration.

    The Journal of biological chemistry 2007;282;32;23491-9

  • Intrafamilial clinical heterogeneity associated with a novel mutation of the retinal degeneration slow/peripherin gene.

    Simonelli F, Testa F, Marini V, Interlandi E, Rossi S, Pognuz DR, Virgili G, Garrè C and Bandello F

    Department of Ophthalmology, Second University of Naples, Naples, Italy. franctes@tin.it

    Aims: To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene.

    Methods: Ten family members underwent ophthalmologic assessment with slit-lamp biomicroscopy, dilated fundus examination, fundus photography, autofluorescence imaging and electrophysiological tests. Genomic DNA was extracted from blood samples of all family members (n = 15) using the standard salting-out procedure.

    Results: The novel C165R mutation was identified in 8 individuals. Of these 8 patients, only 6 gave consent to the clinical study. They had a retinal disease characterized by an adulthood onset of symptoms, and their best corrected visual acuity was between 20/50 and 20/20. Fundus examination showed that 3 patients had typical fundus flavimaculatus: 1 had butterfly-shaped pattern dystrophy and 2 had incipient retinal changes.

    Conclusion: We identified a novel mutation of the retinal degeneration slow/peripherin gene in a family affected by different patterns of retinal dystrophy. This is the first report of an association of fundus flavimaculatus with butterfly-shaped pattern dystrophy.

    Ophthalmic research 2007;39;5;255-9

  • Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin.

    Millecamps S, Robertson J, Lariviere R, Mallet J and Julien JP

    Research Centre of Centre Hospitalier Universitaire de Québec, Department of Anatomy and Physiology of Laval University, Quebec, Canada.

    Peripherin is a type III neuronal intermediate filament detected in motor neuron inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously reported that overexpression of peripherin provokes late-onset motor neuron dysfunction in transgenic mice. Here, we show that peripherin overexpression slows down axonal transport of neurofilament (NF) proteins, and that the transport defect precedes by several months the appearance of axonal spheroids in adult mice. Defective NF transport by peripherin up-regulation was further confirmed with dorsal root ganglia (DRG) neurons cultured from peripherin transgenic embryos. Immunofluorescence microscopy and western blotting revealed that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H species in DRG neurites. Similarly the transport of a green fluorescent protein (GFP)-tagged NF-M, delivered by means of a lentiviral construct, was impaired in DRG neurites overexpressing peripherin. These results demonstrate that peripherin overexpression can cause defective transport of type IV NF proteins, a phenomenon that may account for the progressive formation of ALS-like spheroids in axons.

    Journal of neurochemistry 2006;98;3;926-38

  • Towards a proteome-scale map of the human protein-protein interaction network.

    Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP and Vidal M

    Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

    Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

    Funded by: NCI NIH HHS: R33 CA132073; NHGRI NIH HHS: P50 HG004233, R01 HG001715, RC4 HG006066, U01 HG001715; NHLBI NIH HHS: U01 HL098166

    Nature 2005;437;7062;1173-8

  • A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis.

    Gros-Louis F, Larivière R, Gowing G, Laurent S, Camu W, Bouchard JP, Meininger V, Rouleau GA and Julien JP

    Centre for Research in Neuroscience, McGill University Health Centre, Montreal General Hospital Research Institute, Montreal, Québec H3G 1A4, Canada.

    Peripherin is a neuronal intermediate filament associated with inclusion bodies in motor neurons of patients with amyotrophic lateral sclerosis (ALS). A possible peripherin involvement in ALS pathogenesis has been suggested based on studies with transgenic mouse overexpressors and with a toxic splicing variant of the mouse peripherin gene. However, the existence of peripherin gene mutations in human ALS has not yet been documented. Therefore, we screened for sequence variants of the peripherin gene (PRPH) in a cohort of ALS patients including familial and sporadic cases. We identified 18 polymorphic variants of PRPH detected in both ALS and age-matched control populations. Two additional PRPH variants were discovered in ALS cases but not in 380 control individuals. One variant consisted of a nucleotide insertion in intron 8 (PRPH(IVS8)(-36insA)), whereas the other one consisted of a 1-bp deletion within exon 1 (PRPH(228delC)), predicting a truncated peripherin species of 85 amino acids. Remarkably, expression of this frameshift peripherin mutant in SW13 cells resulted in disruption of neurofilament network assembly. These results suggest that PRPH mutations may be responsible for a small percentage of ALS, cases and they provide further support of the view that neurofilament disorganization may contribute to pathogenesis.

    The Journal of biological chemistry 2004;279;44;45951-6

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Expression of peripherin in ubiquinated inclusions of amyotrophic lateral sclerosis.

    He CZ and Hays AP

    Department of Pathology, College of Physicians and Surgeons, Columbia University, PH 15th Stem, Room 124, 630 West 168th Street, New York, NY 10032, USA.

    We evaluated the expression of the type III intermediate filament (IF) protein, peripherin (PRP), in ubiquinated inclusions of motor neurons in amyotrophic lateral sclerosis (ALS). A previous study showed that overexpression of PRP in transgenic mice induces motor neuron disease with formation of PRP-containing inclusions before onset of symptoms [J. Cell Biol. 147 (3) (1999) 531]. To determine whether PRP inclusions occur in the human disease, we applied doublelabeling immunofluorescence to paraffin sections of the spinal cord obtained by autopsy of 40 ALS patients with sporadic disease and 39 controls. Inclusions that expressed immunoreactive ubiquitin and peripherin were recorded by video camera, and the sections were stained by hematoxylin and eosin (H&E) to define morphology. Lewy body-like inclusions (LBLIs) were seen in motor neuron perikarya of 9 of 40 ALS cases and none in controls; all LBLIs expressed peripherin. Skein-like inclusions (SLIs) were identified by ubiquitin, but did not express PRP with rare exceptions. Neither skein-like inclusions nor LBLIs expressed alpha B-crystallin, neurofilament protein (NF-L, NF-M and NF-H subunits), alpha-internexin, actin or alpha-synuclein. Immunoblot of the whole spinal cord exhibited a single 57-kDa band of peripherin in ALS patients and controls. Our data document the expression of peripherin in LBLIs, which may provide a clue to the pathogenesis of neurodegeneration in ALS.

    Journal of the neurological sciences 2004;217;1;47-54

  • Complete sequencing and characterization of 21,243 full-length human cDNAs.

    Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S

    Helix Research Institute, 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan.

    As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

    Nature genetics 2004;36;1;40-5

  • Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density.

    Rao MV, Engle LJ, Mohan PS, Yuan A, Qiu D, Cataldo A, Hassinger L, Jacobsen S, Lee VM, Andreadis A, Julien JP, Bridgman PC and Nixon RA

    Center for Dementia Research, Nathan Kline Institute, NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.

    The identification of molecular motors that modulate the neuronal cytoskeleton has been elusive. Here, we show that a molecular motor protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves. Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand. A physiological association is indicated by observations that the level of myosin Va is reduced in axons of NF-L-null mice lacking neurofilaments and increased in mice overexpressing NF-L, but unchanged in NF-H-null mice. In vivo pulse-labeled myosin Va advances along axons at slow transport rates overlapping with those of neurofilament proteins and actin, both of which coimmunoprecipitate with myosin Va. Eliminating neurofilaments from mice selectively accelerates myosin Va translocation and redistributes myosin Va to the actin-rich subaxolemma and membranous organelles. Finally, peripheral axons of dilute-lethal mice, lacking functional myosin Va, display selectively increased neurofilament number and levels of neurofilament proteins without altering axon caliber. These results identify myosin Va as a neurofilament-associated protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons.

    Funded by: NIA NIH HHS: 2T32 AG 00222, AG 05604, R01 AG005604, R37 AG005604, T32 AG000222; NIDDK NIH HHS: P30 DK 19525, P30 DK019525

    The Journal of cell biology 2002;159;2;279-90

  • Desmoplastic and spindle cell melanomas express protein markers of the neural crest but not of later committed stages of Schwann cell differentiation.

    Huttenbach Y, Prieto VG and Reed JA

    Section of Dermatopathology, Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.

    Background: The rare desmoplastic and spindle cell variants of malignant melanoma exhibit histological and biochemical features suggestive of early Schwann cell differentiation. These features include a spindle-shaped morphology, neurotropism, and the expression of the low affinity nerve growth factor receptor (p75NGFR).

    Methods: We evaluated by immunohistochemistry (using formalin-fixed, paraffin-embedded tissues) nine desmoplastic and three spindle cell melanomas for the expression of peripherin, p75NGFR, neural cell adhesion molecule (CD56/N-CAM), and growth-associated phosphoprotein-43 (GAP-43). Peripherin is expressed in the neural crest and in neurons, but not in cells committed to the Schwann cell lineage. p75NGFR and CD56/N-CAM also are expressed in early neural crest cells, but persist in unmyelinated and early premyelinating Schwann cells. GAP-43 is expressed in unmyelinated Schwann cells, but is downregulated in the later premyelinating to promyelinating stages of cells committed to the Schwann cell lineage.

    Results: Peripherin was expressed in 7/12 (58%), p75NGFR in 4/12 (33%), and CD56/N-CAM in 6/12 (50%) of the desmoplastic and spindle cell melanomas. GAP-43 was not expressed (0%) in any of the 12 melanomas (chi2, p = 0.05).

    Conclusions: Desmoplastic and spindle cell melanomas express protein markers common to cells of the neural crest and to neurons similar to the immunophenotype previously reported for epithelioid cell melanomas. The expression of peripherin and the lack of expression of GAP-43 further define that these rare subtypes of melanoma do not recapitulate the later committed stages of Schwann cell differentiation.

    Funded by: NCI NIH HHS: CA79872

    Journal of cutaneous pathology 2002;29;9;562-8

  • Intron 1 is required for cell type-specific, but not injury-responsive, peripherin gene expression.

    Uveges TE, Shan Y, Kramer BE, Wight DC and Parysek LM

    Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati, Cincinnati, Ohio 45267-0521, USA.

    The "primitive" neurons of the peripheral nervous system (PNS) have the remarkable ability to regenerate new fibers. This regenerative process requires a sequence of gene activation and repression that is poorly understood. One gene that is almost exclusively expressed in neurons of the PNS and is activated after nerve injury is the peripherin intermediate filament gene, but little is known about the genomic elements that control either its restricted expression or its response to nerve injury in adult mice. Previous studies suggested that both 5' flanking sequence and intragenic regions were required for cell type-specific and injury-specific expression. To determine which intragenic regions were critical, mice were generated that expressed peripherin transgenes lacking different introns. Analyses of these mice revealed that deletion of introns 2-8 had no effect on either the cell type-specific or injury-specific expression of the peripherin gene; however, the remaining intron, intron 1, differentially bound Sp1 transcription-related proteins/protein complexes in extracts from peripherin-expressing and nonexpressing tissues. Furthermore, a transgene that lacked intron 1 was not expressed in many neurons that contain endogenous peripherin but was activated after injury. Thus, accurate cell type-specific peripherin gene expression in the PNS depends on elements within intron 1, but other sequences, most likely in the 5'flanking region, are required for activating the peripherin gene in response to nerve injury.

    Funded by: PHS HHS: 35313

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2002;22;18;7959-67

  • Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation.

    Boerkoel CF, Takashima H, Garcia CA, Olney RK, Johnson J, Berry K, Russo P, Kennedy S, Teebi AS, Scavina M, Williams LL, Mancias P, Butler IJ, Krajewski K, Shy M and Lupski JR

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

    Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder that has been associated with alterations of several proteins: peripheral myelin protein 22, myelin protein zero, connexin 32, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1 product, neurofilament light chain, and kinesin 1B. To determine the frequency of mutations in these genes among patients with CMT or a related peripheral neuropathy, we identified 153 unrelated patients who enrolled prior to the availability of clinical testing, 79 had a 17p12 duplication (CMT1A duplication), 11 a connexin 32 mutation, 5 a myelin protein zero mutation, 5 a peripheral myelin protein 22 mutation, 1 an early growth response factor 2 mutation, 1 a periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilament light chain mutation, and 50 had no identifiable mutation; the N-myc downstream regulated gene 1 and the kinesin 1B gene were not screened for mutations. In the process of screening the above cohort of patients as well as other patients for CMT-causative mutations, we identified several previously unreported mutant alleles: two for connexin 32, three for myelin protein zero, and two for peripheral myelin protein 22. The peripheral myelin protein 22 mutation W28R was associated with CMT1 and profound deafness. One patient with a CMT2 clinical phenotype had three myelin protein zero mutations (I89N+V92M+I162M). Because one-third of the mutations we report arose de novo and thereby caused chronic sporadic neuropathy, we conclude that molecular diagnosis is a necessary adjunct for clinical diagnosis and management of inherited and sporadic neuropathy.

    Funded by: NIDDK NIH HHS: K08 DK02738; NINDS NIH HHS: R01 NS27042

    Annals of neurology 2002;51;2;190-201

  • Expression of the intermediate filament peripherin in extraskeletal myxoid chondrosarcoma.

    Cummings TJ, Shea CR, Reed JA, Burchette JL and Prieto VG

    Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

    The embryologic histogenesis of cartilage is not well characterized. While cranial cartilage is believed to be derived from pluripotential precursor cells of the neural crest, chondrocytes found elsewhere in the body are thought to be derived from mesoderm. As such, soft tissue tumors with cartilaginous differentiation may be related to neural crest or mesoderm. Peripherin is an intermediate filament encoded on chromosome 12, involved in growth and development of the peripheral nervous system. Peripherin is apparently expressed exclusively in cells derived from the neural crest and neural tube. A group of six soft tissue tumor types was selected because they are either of controversial differentiation or cytogenetically related to chromosome 12. A total of 41 cases was evaluated with antibodies against the intermediate filament peripherin. A panel of neural and neuroendocrine differentiation markers was used in selected cases. Three of five extraskeletal myxoid chondrosarcomas showed strong cytoplasmic reactivity with anti-peripherin. No peripherin expression was noted in any of eleven epithelioid sarcomas, eight liposarcomas, seven conventional chondrosarcomas, four neurothekeomas, three alveolar soft part sarcomas, or three clear cell sarcomas. The finding of peripherin expression in some extraskeletal myxoid chondrosarcomas may suggest the ability of some tumors to demonstrate both neural and chondroid differentiation.

    Journal of cutaneous pathology 2000;27;3;141-6

  • Disulfide-mediated oligomerization of Peripherin/Rds and Rom-1 in photoreceptor disk membranes. Implications for photoreceptor outer segment morphogenesis and degeneration.

    Loewen CJ and Molday RS

    Department of Biochemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

    Peripherin/Rds is a tetraspanning membrane protein that has been implicated in photoreceptor outer segment morphogenesis and inherited retinal degenerative diseases. Together with the structurally related protein, Rom-1, it forms a complex along the rims of rod and cone disc membranes. We have compared the oligomeric structure of these proteins from nonreduced and dithiothreitol reduced membranes by velocity sedimentation, SDS-gel electrophoresis, immunoaffinity chromatography, and chemical cross-linking. Under reducing conditions peripherin/Rds and Rom-1 existed as homomeric and heteromeric core complexes devoid of intermolecular disulfide bonds. Under nonreducing conditions core complexes associated through intermolecular disulfide bonds to form oligomers. One intermediate-size oligomer contained monomers and disulfide-linked dimers of peripherin/Rds and Rom-1, while larger oligomers consisted only of disulfide-linked peripherin/Rds dimers when analyzed on nonreducing SDS gels. Consistent with this result, disc membranes contained twice as much peripherin/Rds as Rom-1. Peripherin/Rds individually expressed in COS-1 cells also formed disulfide-linked oligomers bridged through Cys-150 residues, whereas Rom-1 showed little tendency to form oligomers. These results indicate that peripherin/Rds and Rom-1 associate noncovalently to form multisubunit core complexes. Peripherin/Rds containing core complexes interact through specific intermolecular disulfide bonds to form oligomers which may play a crucial role in photoreceptor disc morphogenesis and retinal degenerative diseases.

    Funded by: NEI NIH HHS: EY 2422

    The Journal of biological chemistry 2000;275;8;5370-8

  • Peripherin is tyrosine-phosphorylated at its carboxyl-terminal tyrosine.

    Angelastro JM, Ho CL, Frappier T, Liem RK and Greene LA

    Department of Pathology and Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.

    Peripherin is a type III intermediate filament present in peripheral and certain CNS neurons. We report here that peripherin contains a phosphotyrosine residue and, as such, is the only identified intermediate filament protein known to be modified in this manner. Antiserum specific for phosphotyrosine recognizes peripherin present in PC12 cells (with or without nerve growth factor treatment) and in rat sciatic nerve as well as that expressed in Sf-9 cells and SW-13 cl. 2 vim- cells. The identity of peripherin as a tyrosine-phosphorylated protein in PC12 cells was confirmed by immunoprecipitation, two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, and phosphoamino acid analysis. Unlike serine/threonine phosphorylation, tyrosine phosphorylation of peripherin is not regulated by depolarization or nerve growth factor treatment. To identify the site of tyrosine phosphorylation, rat peripherin was mutated at several tyrosine residues and expressed in SW-13 cl. 2 vim- cells. Tyrosine phosphorylation was selectively lost only for peripherin mutants in which the carboxy-terminal tyrosine (Y474) was mutated. Indirect immunofluorescence staining indicated that both wild-type peripherin and peripherin Y474F form a filamentous network in SW-13 cl. 2 vim- cells. This indicates that tyrosine phosphorylation of the peripherin C-terminal residue is not required for assembly and leaves open the possibility that this modification serves other functions.

    Journal of neurochemistry 1998;70;2;540-9

  • Differential expression of the intermediate filament peripherin in cutaneous neural lesions and neurotized melanocytic nevi.

    Prieto VG, McNutt NS, Lugo J and Reed JA

    Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.

    Peripherin is an intermediate filament involved in growth and development of the peripheral nervous system, and is produced by neurons and the beta cells of the islets of Langerhans. Recently, malignant melanomas and some melanocytic nevi have been shown to express peripherin. It is unknown if Schwann cells, also derived from the neural crest, express peripherin. Expression of peripherin was evaluated by immunohistochemistry in cutaneous lesions characterized by a prominent Schwann cell component including 26 neurofibromas (NF), 10 schwannomas (SCH), seven granular cell tumors, and five palisaded encapsulated neuromas (PEN); 13 neurotized melanocytic nevi (NMN) also were evaluated because these lesions contain Wagner-Meissnerlike structures and type C nevus cells, which exhibit a "schwannian" phenotype. Peripherin was detected in the axons of normal peripheral nerves. NF and PEN contained numerous axons dispersed throughout the lesions, whereas only scattered small nerves were seen in GCT. In SCH, only rare axons were labeled, mostly at the periphery of the lesions. All other cells in these four types of lesions, therefore including Schwann cells, were not labeled. In most NMN, labeled axons were identified within the lesions. In a few cases, rare epithelioid melanocytes within the superficial portions of the nevi were labeled. The Wagner-Meissnerlike structures and type C nevus cells (schwannian) were not labeled in any lesion; however, numerous labeled axons invested these areas. Because there are different relative numbers of peripherin-labeled axons throughout NF, PEN, some nevi, and SCH, analysis of peripherin expression may be helpful in the diagnosis of these lesions. Neurons and some epithelioid melanocytes, in contrast to type C nevus cells and Schwann cells of NF and SCH, express peripherin, providing further evidence for a transition from a more neuronal to a more schwannian phenotype during the normal maturation sequence of melanocytes in nevi.

    The American journal of surgical pathology 1997;21;12;1450-4

  • The intermediate filament peripherin is expressed in cutaneous melanocytic lesions.

    Prieto VG, McNutt NS, Lugo J and Reed JA

    Department of Pathology, New York-Hospital-Cornell Medical Center, New York 10021, USA.

    Peripherin is an intermediate filament involved in growth and development of the peripheral nervous system and is localized to neurons, some other cells derived from neural tube and neural crest, and some neuroendocrine cells (e.g. beta cells of islets of Langerhans). Peripherin also has been demonstrated in neuroblastomas and cutaneous neuroendocrine (Merkel cell) carcinomas. The expression of peripherin by other cells derived from the neural crest is unknown. We evaluated by immunohistochemistry 74 cutaneous melanocytic lesions including primary invasive malignant melanoma (IMM), melanoma in situ (MIS), atypical nevus (nevus with architectural disorder and cytologic atypia of melanocytes) (AN), spindle and epithelioid cell nevus (Spitz nevus) (SN), blue nevus (BN), and common intradermal benign melanocytic nevus (BMN) for expression of peripherin. Peripherin was detected in a cytoplasmic distribution within tumor cells in 14/14 IMM and 8/10 MIS. For IMM, peripherin localized to both the intraepidermal and invasive dermal components. Peripherin was detected in 10/10 AN and 9/9 SN, being localized to the intraepidermal component and, focally, to the superficial dermal component of the lesions. The dendritic nevus cells in 15/15 BN also expressed peripherin. For most of the BMN, expression of peripherin was absent or limited to rare, scattered cells in the superficial portion of the lesions. Melanocytes in adjacent normal skin were not labeled in any of the lesions studied. These results indicate that expression of peripherin is common in both benign and malignant melanocytic lesions, but not in normal resting adult melanocytes. Among benign lesions, expression of peripherin in the dermal component is rare except in the dendritic cells of BN. These findings provide evidence that the expression of peripherin, a marker of neuronal differentiation, is maintained by IMM, MIS, and BN, but is lost in the normal maturational sequence of the dermal component of other melanocytic lesions.

    Journal of cutaneous pathology 1997;24;3;145-50

  • Transcriptional activation of the neuronal peripherin-encoding gene depends on a G + C-rich element that binds Sp1 in vitro and in vivo.

    Ferrari N, Desmarais D and Royal A

    Département de Pathologie, Université de Montréal, Québec, Canada.

    Peripherin (Prph) is a type-III intermediate filament (IF) protein principally synthesized in peripheral nervous system neurons. We have previously shown that three regulatory elements, PER1, PER2 and PER3, in the first 98 bp of the Prph gene promoter, were sufficient to direct cell-type specific expression of a reporter gene [Desmarais et al., EMBO J. 11 (1992) 2971-2980]. Of these elements, PER1 was found to be important for cell-type specificity, but required the presence of other elements for transcriptional activity. Here, we show that PER3 is a stronger activator than PER2 and that it can stimulate cell-type-specific transcription when combined with PER1. We have characterized the G + C-rich PER3 element for its ability to bind trans-acting factors. Gel retardation and methylation interference (MI) assays show that PER3 binds transcription factor Sp1. In addition, an anti-Sp1 antibody recognizes the PER3 DNA-binding protein. A 3-bp mutation abrogating the capacity of PER3 to bind Sp1 in vitro completely abolished expression of the reporter gene construct containing only PER3 and PER1, while in a construct containing the first 256 bp of the Prph promoter, it led to an 80% decrease with respect to the control wild-type construct. Finally, by co-transfection of a Sp1-expressing plasmid, we show that Sp1 can stimulate transcription from a reporter gene containing the PER3 sequence. Together, these results indicate that interactions between Sp1 and the proteins binding PER1 are involved in the control of the Prph gene.

    Gene 1995;159;2;159-65

  • The structure of the human peripherin gene (PRPH) and identification of potential regulatory elements.

    Foley J, Ley CA and Parysek LM

    Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Ohio 45267-0521.

    We determined the complete nucleotide sequence of the coding region of the human peripherin gene (PRPH), as well as 742 bp 5' to the cap site and 584 bp 3' to the stop codon, and compared its structure and sequence to the rat and mouse genes. The overall structure of 9 exons separated by 8 introns is conserved among these three mammalian species. The nucleotide sequences of the human peripherin gene exons were 90% identical to the rat gene sequences, and the predicted human peripherin protein differed from rat peripherin at only 18 of 475 amino acid residues. Comparison of the 5' flanking regions of the human peripherin gene and rodent genes revealed extensive areas of high homology. Additional conserved segments were found in introns 1 and 2. Within the 5' region, potential regulatory sequences, including a nerve growth factor negative regulatory element, a Hox protein binding site, and a heat shock element, were identified in all peripherin genes. The positional conservation of each element suggests that they may be important in the tissue-specific, developmental-specific, and injury-specific expression of the peripherin gene.

    Funded by: NICHD NIH HHS: NICHD (25752)

    Genomics 1994;22;2;456-61

  • Distribution of cytoskeletal proteins (neurofilaments, peripherin and MAP-tau) in the cochlea of the human fetus.

    Després G, Leger GP, Dahl D and Romand R

    Laboratoire de Neurobiologie et Physiologie du Développement, Université Blaise Pascal, Aubière, France.

    We report here an immunohistochemical study of the distribution of intermediate filaments (neurofilament, peripherin) and a microtubule-associated protein, tau, in the human fetal cochlea at 27 weeks of gestation. Neurofilament immunoreactivity (160 and 200 KDa) was localized in afferent and efferent fibers of the cochlear innervation and restricted to a few small spiral ganglion neurons. Peripherin immunoreactivity was specifically distributed in some small ganglion neurons and in their central and peripheral extensions, particularly in fibers reaching the lower part of the outer hair cells. Double immuno-labelling studies with these neurofilaments and peripherin antibodies show that only small neuron cell bodies were stained. Morpholometrical data indicate that immunostained neurons could be related to the Type II neuron population in the spiral ganglion. Tau protein was localized in intraganglionic spiral bundle fibers and in fibers that reach the lower part of hair cells. These observations suggest that neurofilament and peripherin antibodies stain a particular population of human spiral ganglion neurons with Type II characteristics. Moreover, the specificity of peripherin labelling in Type II cells and their processes suggest that peripherin could be used as a probe for the developmental study of this system in the human cochlea. On the other hand, tau antibody appeared as a marker for efferent fibers during development and could give information on the ontogenesis of efferent innervation.

    Acta oto-laryngologica 1994;114;4;377-81

  • Expression and distribution of peripherin protein in human neuroblastoma cell lines.

    Pedersen WA, Becker LE and Yeger H

    Department of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.

    A series of human neuroblastoma (NB) cell lines was analyzed for expression of peripherin, a class-III intermediate filament protein expressed at high levels in ganglia of the peripheral nervous system. By Western blotting, peripherin protein was detected in all human NB cell lines examined. The highest level of peripherin was found in the NUB-7 cell line, previously characterized as homogeneously neuroblastic. By immunofluorescence labeling, peripherin was shown to be organized in a perinuclear filamentous pattern and, exemplified by IMR32 cells, was also shown to be localized to spontaneously formed neurites. Peripherin was expressed in neuroblastic but not substrate-adherent cells, and was found at low levels in I-type cells. There was a pronounced redistribution of peripherin to neurites formed in response to dibutyryl cyclic adenosine monophosphate (dbcAMP) and all-trans-retinoic acid (RA). In NUB-7 cells, which do not extend neurites in response to nerve growth factor, there was no change in the level of peripherin protein following treatment with this agent. Both dbcAMP and RA induced a redistribution of peripherin to neurite extensions, but only treatment with RA increased the level of the protein as demonstrated with NUB-6A4 and NUB-6C4 subclones. Peripherin was also variably expressed in peripheral neuroepithelioma (NE) cell lines tested, but was organized into a more basket-like filamentous pattern in these cells. The heterogeneous expression and distribution of peripherin in NB and NE cell lines indicate that this protein is associated with maturation of the neuronal phenotype and hence serves as a differentiation marker for tumors derived from the neural crest.

    International journal of cancer 1993;53;3;463-70

  • Chromosomal localisation of the mouse and human peripherin genes.

    Moncla A, Landon F, Mattei MG and Portier MM

    Centre de Génétique médicale, Institut National de la Santé et de la Recherche Médicale U242, Hôpital d'enfants de la Timone, Marseille, France.

    Using a mouse cDNA probe encoding for the major part of peripherin, a type III intermediate filament protein, we have assigned, by in situ hybridization, the mouse and human peripherin genes, Prph, to the E-F region of chromosome 15 and to the q12-q13 region of chromosome 12, respectively. These regions are known as homologous chromosomal segments containing other intermediate filament genes (keratins) and also other genes which could be co-ordinately regulated.

    Genetical research 1992;59;2;125-9

  • Network antibodies identify nuclear lamin B as a physiological attachment site for peripherin intermediate filaments.

    Djabali K, Portier MM, Gros F, Blobel G and Georgatos SD

    College de France, Biochimie Cellulaire, Paris.

    We studied the molecular associations between peripherin (a neuronal, type III intermediate filament subunit) and nuclear lamins. We show here that isolated peripherin binds selectively to mammalian lamin B under in vitro conditions. We further demonstrate that a synthetic peptide, representing the proximal part of peripherin's tail domain (P1), also associates with mammalian lamin B in a saturable, cooperative, and specific fashion. Laboratory animals immunized with P1 spontaneously develop idiotypic and anti-idiotypic antibodies recognizing peripherin and lamin B, respectively. These data provide essentially in vivo evidence that lamin B represents a constitutive nuclear "receptor" site for the tail domains of peripherin intermediate filaments.

    Cell 1991;64;1;109-21

OMIM - other

Gene lists (5)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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