G2Cdb::Gene report

Gene id
G00000668
Gene symbol
Ap1b1 (MGI)
Species
Mus musculus
Description
adaptor protein complex AP-1, beta 1 subunit
Orthologue
G00001917 (Homo sapiens)

Databases (9)

Curated Gene
OTTMUSG00000005076 (Vega mouse gene)
Gene
ENSMUSG00000009090 (Ensembl mouse gene)
11764 (Entrez Gene)
1084 (G2Cdb plasticity & disease)
Gene Expression
MGI:1096368 (Allen Brain Atlas)
11764 (Genepaint)
Literature
600157 (OMIM)
Marker Symbol
MGI:1096368 (MGI)
Protein Sequence
O35643 (UniProt)

Synonyms (2)

  • Adtb1
  • beta-prime adaptin

Literature (21)

Pubmed - other

  • A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

    Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I, Lin-Marq N, Koch M, Bilio M, Cantiello I, Verde R, De Masi C, Bianchi SA, Cicchini J, Perroud E, Mehmeti S, Dagand E, Schrinner S, Nürnberger A, Schmidt K, Metz K, Zwingmann C, Brieske N, Springer C, Hernandez AM, Herzog S, Grabbe F, Sieverding C, Fischer B, Schrader K, Brockmeyer M, Dettmer S, Helbig C, Alunni V, Battaini MA, Mura C, Henrichsen CN, Garcia-Lopez R, Echevarria D, Puelles E, Garcia-Calero E, Kruse S, Uhr M, Kauck C, Feng G, Milyaev N, Ong CK, Kumar L, Lam M, Semple CA, Gyenesei A, Mundlos S, Radelof U, Lehrach H, Sarmientos P, Reymond A, Davidson DR, Dollé P, Antonarakis SE, Yaspo ML, Martinez S, Baldock RA, Eichele G and Ballabio A

    Telethon Institute of Genetics and Medicine, Naples, Italy.

    Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

    Funded by: Medical Research Council: MC_U127527203; Telethon: TGM11S03

    PLoS biology 2011;9;1;e1000582

  • Proteomics analysis identifies phosphorylation-dependent alpha-synuclein protein interactions.

    McFarland MA, Ellis CE, Markey SP and Nussbaum RL

    National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20891, USA.

    Mutations and copy number variation in the SNCA gene encoding the neuronal protein alpha-synuclein have been linked to familial Parkinson disease (Thomas, B., and Beal, M. F. (2007) Parkinson's disease. Hum. Mol. Genet. 16, R183-R194). The carboxyl terminus of alpha-synuclein can be phosphorylated at tyrosine 125 and serine 129, although only a small fraction of the protein is phosphorylated under normal conditions (Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba, M., Iwatsubo, T., Meijer, L., Kahle, P. J., and Haass, C. (2000) Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J. Biol. Chem. 275, 390-397). Under pathological conditions, such as in Parkinson disease, alpha-synuclein is a major component of Lewy bodies, a pathological hallmark of Parkinson disease, and is mostly phosphorylated at Ser-129 (Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J. P., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X. F., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai, W. P., and Chilcote, T. J. (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739-29752). Controversy exists over the extent to which phosphorylation of alpha-synuclein and/or the visible protein aggregation in Lewy bodies are steps in disease pathogenesis, are protective, or are neutral markers for the disease process. Here we used the combination of peptide pulldown assays and mass spectrometry to identify and compare protein-protein interactions of phosphorylated and non-phosphorylated alpha-synuclein. We showed that non-phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not. Instead the set of proteins pulled down by phosphorylated alpha-synuclein was highly enriched in certain cytoskeletal proteins, in vesicular trafficking proteins, and in a small number of enzymes involved in protein serine phosphorylation. This targeted comparative proteomics approach for unbiased identification of protein-protein interactions suggests that there are functional consequences when alpha-synuclein is phosphorylated.

    Funded by: Intramural NIH HHS; NIMH NIH HHS: Z01 MH000279

    Molecular & cellular proteomics : MCP 2008;7;11;2123-37

  • EUCOMM--the European conditional mouse mutagenesis program.

    Friedel RH, Seisenberger C, Kaloff C and Wurst W

    GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.

    Functional analysis of the mammalian genome is an enormous challenge for biomedical scientists. To facilitate this endeavour, the European Conditional Mouse Mutagenesis Program (EUCOMM) aims at generating up to 12 000 mutations by gene trapping and up to 8000 mutations by gene targeting in mouse embryonic stem (ES) cells. These mutations can be rendered into conditional alleles, allowing Cre recombinase-mediated disruption of gene function in a time- and tissue-specific manner. Furthermore, the EUCOMM program will generate up to 320 mouse lines from the EUCOMM resource and up to 20 new Cre driver mouse lines. The EUCOMM resource of vectors, mutant ES cell lines and mutant mice will be openly available to the scientific community. EUCOMM will be one of the cornerstones of an international effort to create a global mouse mutant resource.

    Briefings in functional genomics & proteomics 2007;6;3;180-5

  • The gamma/sigma1 and alpha/sigma2 hemicomplexes of clathrin adaptors AP-1 and AP-2 harbor the dileucine recognition site.

    Doray B, Lee I, Knisely J, Bu G and Kornfeld S

    Department of Internal Medicine and Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.

    The clathrin adaptors AP-1 and AP-2 bind cargo proteins via two types of motifs: tyrosine-based Yxx phi and dileucine-based [DE]XXXL[LI]. Although it is well established that Yxx phi motifs bind to the mu subunits of AP-1 or AP-2, dileucine motifs have been reported to bind to either the mu or beta subunits of these adaptors as well as the gamma/sigma1 hemicomplex of AP-1. To clarify this controversy, the various subunits of AP-1 and AP-2 were expressed individually and in hemicomplex form in insect cells, and they were used in glutathione S-transferase pull-down assays to determine their binding properties. We report that the gamma/sigma1 or alpha/sigma2 hemicomplexes bound the dileucine-based motifs of several proteins quite strongly, whereas binding by the beta1/mu1 and beta2/mu2 hemicomplexes, and the individual beta or mu subunits, was extremely weak or undetectable. The gamma/sigma1 and alpha/sigma2 hemicomplexes displayed substantial differences in their preference for particular dileucine-based motifs. Most strikingly, an aspartate at position -4 compromised binding to the gamma/sigma1 hemicomplex, whereas minimally affecting binding to alpha/sigma2. There was an excellent correlation between binding to the alpha/sigma2 hemicomplex and in vivo internalization mediated by the dileucine-based sorting signals. These findings provide new insights into the trafficking mechanisms of D/EXXXL[LI]-mediated sorting signals.

    Funded by: NCI NIH HHS: CA-08759, R37 CA008759

    Molecular biology of the cell 2007;18;5;1887-96

  • Beta-adaptin: key molecule for microglial scavenger receptor function under oxidative stress.

    Manzano-León N, Delgado-Coello B, Guaderrama-Díaz M and Mas-Oliva J

    Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, DF, Mexico.

    Scavenger receptors internalize chemically modified low density lipoprotein particles (ac-LDL) and other ligands through the process of receptor-mediated endocytosis. During this investigation using amyloid-beta as a natural ligand for the SR, we studied under a ligand-induced oxidative stress condition, changes in protein expression of several adaptor proteins important in the organization of the endocytic machinery in microglia and macrophages. Differential expression experiments of beta-adaptin, alpha-adaptin, SR-AI, and SR-BI in RAW (macrophages) and EOC (microglia) cells were performed according to dosage and exposure time to amyloid-beta. Our results show that according to dosage, amyloid-beta produces an oxidative stress state that importantly affects the availability of beta-adaptin. Under these conditions, RT-PCR assays show that beta-adaptin mRNA is normally synthesized, reason why protein translation or protein structure of beta-adaptin might be altered. These observations might have impact in the understanding of the mechanisms microglia employ to process amyloid-beta in the brain.

    Biochemical and biophysical research communications 2006;351;3;588-94

  • Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease.

    Sacksteder CA, Qian WJ, Knyushko TV, Wang H, Chin MH, Lacan G, Melega WP, Camp DG, Smith RD, Smith DJ, Squier TC and Bigelow DJ

    Cell Biology and Biochemistry Group, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.

    Increased abundance of nitrotyrosine modifications of proteins have been documented in multiple pathologies in a variety of tissue types and play a role in the redox regulation of normal metabolism. To identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic data set identifying 7792 proteins from a whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in the identification of 31 unique nitrotyrosine sites within 29 different proteins. More than half of the nitrated proteins that have been identified are involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces an increased level of nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high-resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, a characteristic consistent with peroxynitrite-induced tyrosine modification. In addition, most sequences contain cysteines or methionines proximal to nitrotyrosines, contrary to suggestions that these amino acid side chains prevent tyrosine nitration. More striking is the presence of a positively charged moiety near the sites of nitration, which is not observed for non-nitrated tyrosines. Together, these observations suggest a predictive tool of functionally important sites of nitration and that cellular nitrating conditions play a role in neurodegenerative changes in the brain.

    Funded by: NCRR NIH HHS: RR018522; NIA NIH HHS: AG12993, AG18013; NIDA NIH HHS: DA015802; NINDS NIH HHS: NS050148

    Biochemistry 2006;45;26;8009-22

  • Identification of novel CBP interacting proteins in embryonic orofacial tissue.

    Yin X, Warner DR, Roberts EA, Pisano MM and Greene RM

    Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Birth Defects Center, ULSD Louisville, KY 40292, USA.

    cAMP response element-binding protein (CREB)-binding protein (CBP) plays an important role as a general co-integrator of multiple signaling pathways and interacts with a large number of transcription factors and co-factors, through its numerous protein-binding domains. To identify nuclear factors associated with CBP in developing orofacial tissue, a yeast two-hybrid screen of a cDNA library derived from orofacial tissue from gestational day 11 to 13 mouse embryos was conducted. Using the carboxy terminus (amino acid residues 1676-2441) of CBP as bait, several novel proteins that bind CBP were identified, including an Msx-interacting-zinc finger protein, CDC42 interaction protein 4/thyroid hormone receptor interactor 10, SH3-domain GRB2-like 1, CCR4-NOT transcription complex subunit 3, adaptor protein complex AP-1 beta1 subunit, eukaryotic translation initiation factor 2B subunit 1 (alpha), and cyclin G-associated kinase. Results of the yeast two-hybrid screen were confirmed by glutathione S-transferase pull-down assays. The identification of these proteins as novel CBP-binding partners allows exploration of new mechanisms by which CBP regulates and integrates diverse cell signaling pathways.

    Funded by: NCRR NIH HHS: P20 RR 017702; NIDCR NIH HHS: R01 DE 05550

    Biochemical and biophysical research communications 2005;329;3;1010-7

  • Libraries enriched for alternatively spliced exons reveal splicing patterns in melanocytes and melanomas.

    Watahiki A, Waki K, Hayatsu N, Shiraki T, Kondo S, Nakamura M, Sasaki D, Arakawa T, Kawai J, Harbers M, Hayashizaki Y and Carninci P

    Genome Science Laboratory, RIKEN, Wako main campus, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan.

    It is becoming increasingly clear that alternative splicing enables the complex development and homeostasis of higher organisms. To gain a better understanding of how splicing contributes to regulatory pathways, we have developed an alternative splicing library approach for the identification of alternatively spliced exons and their flanking regions by alternative splicing sequence enriched tags sequencing. Here, we have applied our approach to mouse melan-c melanocyte and B16-F10Y melanoma cell lines, in which 5,401 genes were found to be alternatively spliced. These genes include those encoding important regulatory factors such as cyclin D2, Ilk, MAPK12, MAPK14, RAB4, melastatin 1 and previously unidentified splicing events for 436 genes. Real-time PCR further identified cell line-specific exons for Tmc6, Abi1, Sorbs1, Ndel1 and Snx16. Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development.

    Nature methods 2004;1;3;233-9

  • 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

  • Wnk1 kinase deficiency lowers blood pressure in mice: a gene-trap screen to identify potential targets for therapeutic intervention.

    Zambrowicz BP, Abuin A, Ramirez-Solis R, Richter LJ, Piggott J, BeltrandelRio H, Buxton EC, Edwards J, Finch RA, Friddle CJ, Gupta A, Hansen G, Hu Y, Huang W, Jaing C, Key BW, Kipp P, Kohlhauff B, Ma ZQ, Markesich D, Payne R, Potter DG, Qian N, Shaw J, Schrick J, Shi ZZ, Sparks MJ, Van Sligtenhorst I, Vogel P, Walke W, Xu N, Zhu Q, Person C and Sands AT

    Lexicon Genetics, 8800 Technology Forest Place, The Woodlands, TX 77381, USA. brian@lexgen.com

    The availability of both the mouse and human genome sequences allows for the systematic discovery of human gene function through the use of the mouse as a model system. To accelerate the genetic determination of gene function, we have developed a sequence-tagged gene-trap library of >270,000 mouse embryonic stem cell clones representing mutations in approximately 60% of mammalian genes. Through the generation and phenotypic analysis of knockout mice from this resource, we are undertaking a functional screen to identify genes regulating physiological parameters such as blood pressure. As part of this screen, mice deficient for the Wnk1 kinase gene were generated and analyzed. Genetic studies in humans have shown that large intronic deletions in WNK1 lead to its overexpression and are responsible for pseudohypoaldosteronism type II, an autosomal dominant disorder characterized by hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Consistent with the human genetic studies, Wnk1 heterozygous mice displayed a significant decrease in blood pressure. Mice homozygous for the Wnk1 mutation died during embryonic development before day 13 of gestation. These results demonstrate that Wnk1 is a regulator of blood pressure critical for development and illustrate the utility of a functional screen driven by a sequence-based mutagenesis approach.

    Proceedings of the National Academy of Sciences of the United States of America 2003;100;24;14109-14

  • Subtractive hybridisation screen identifies sexually dimorphic gene expression in the embryonic mouse gonad.

    McClive PJ, Hurley TM, Sarraj MA, van den Bergen JA and Sinclair AH

    The sex of most mammals is determined by the action of SRY. Its presence initiates testis formation resulting in male differentiation, its absence results in ovary formation and female differentiation. We have used suppression subtraction hybridisation between 12.0-12.5 days postcoitum (dpc) mouse testes and ovaries to identify genes that potentially lie within the Sry pathway. Normalised urogenital ridge libraries comprising 8,352 clones were differentially screened with subtracted probes. A total of 272 candidate cDNAs were tested for qualitative differential expression and localisation by whole mount in situ hybridisation; germ cell-dependent or -independent expression was further resolved using busulfan. Fifty-four genes were identified that showed higher expression in the testis than the ovary. One novel gene may be a candidate for interactions with WT1, based on its localisation to Sertoli cells and map position (16q24.3).

    Genesis (New York, N.Y. : 2000) 2003;37;2;84-90

  • A large-scale, gene-driven mutagenesis approach for the functional analysis of the mouse genome.

    Hansen J, Floss T, Van Sloun P, Füchtbauer EM, Vauti F, Arnold HH, Schnütgen F, Wurst W, von Melchner H and Ruiz P

    Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany.

    A major challenge of the postgenomic era is the functional characterization of every single gene within the mammalian genome. In an effort to address this challenge, we assembled a collection of mutations in mouse embryonic stem (ES) cells, which is the largest publicly accessible collection of such mutations to date. Using four different gene-trap vectors, we generated 5,142 sequences adjacent to the gene-trap integration sites (gene-trap sequence tags; http://genetrap.de) from >11,000 ES cell clones. Although most of the gene-trap vector insertions occurred randomly throughout the genome, we found both vector-independent and vector-specific integration "hot spots." Because >50% of the hot spots were vector-specific, we conclude that the most effective way to saturate the mouse genome with gene-trap insertions is by using a combination of gene-trap vectors. When a random sample of gene-trap integrations was passaged to the germ line, 59% (17 of 29) produced an observable phenotype in transgenic mice, a frequency similar to that achieved by conventional gene targeting. Thus, gene trapping allows a large-scale and cost-effective production of ES cell clones with mutations distributed throughout the genome, a resource likely to accelerate genome annotation and the in vivo modeling of human disease.

    Proceedings of the National Academy of Sciences of the United States of America 2003;100;17;9918-22

  • BayGenomics: a resource of insertional mutations in mouse embryonic stem cells.

    Stryke D, Kawamoto M, Huang CC, Johns SJ, King LA, Harper CA, Meng EC, Lee RE, Yee A, L'Italien L, Chuang PT, Young SG, Skarnes WC, Babbitt PC and Ferrin TE

    Department of Pharmaceutical Chemistry, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

    The BayGenomics gene-trap resource (http://baygenomics.ucsf.edu) provides researchers with access to thousands of mouse embryonic stem (ES) cell lines harboring characterized insertional mutations in both known and novel genes. Each cell line contains an insertional mutation in a specific gene. The identity of the gene that has been interrupted can be determined from a DNA sequence tag. Approximately 75% of our cell lines contain insertional mutations in known mouse genes or genes that share strong sequence similarities with genes that have been identified in other organisms. These cell lines readily transmit the mutation to the germline of mice and many mutant lines of mice have already been generated from this resource. BayGenomics provides facile access to our entire database, including sequence tags for each mutant ES cell line, through the World Wide Web. Investigators can browse our resource, search for specific entries, download any portion of our database and BLAST sequences of interest against our entire set of cell line sequence tags. They can then obtain the mutant ES cell line for the purpose of generating knockout mice.

    Funded by: NCRR NIH HHS: P41 RR001081, P41 RR01081; NHLBI NIH HHS: U01 HL066621, U01 HL66621

    Nucleic acids research 2003;31;1;278-81

  • Transcript map of the Ovum mutant (Om) locus: isolation by exon trapping of new candidate genes for the DDK syndrome.

    Le Bras S, Cohen-Tannoudji M, Guyot V, Vandormael-Pournin S, Coumailleau F, Babinet C and Baldacci P

    Unité Biologie du Développement, CNRS URA 1960, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.

    The DDK syndrome is defined as the embryonic lethality of F1 mouse embryos from crosses between DDK females and males from other strains (named hereafter as non-DDK strains). Genetically controlled by the Ovum mutant (Om) locus, it is due to a deleterious interaction between a maternal factor present in DDK oocytes and the non-DDK paternal pronucleus. Therefore, the DDK syndrome constitutes a unique genetic tool to study the crucial interactions that take place between the parental genomes and the egg cytoplasm during mammalian development. In this paper, we present an extensive analysis performed by exon trapping on the Om region. Twenty-seven trapped sequences were from genes in the databases: beta-adaptin, CCT zeta2, DNA LigaseIII, Notchless, Rad51l3 and Scya1. Twenty-eight other sequences presented similarities with expressed sequence tags and genomic sequences whereas 57 did not. The pattern of expression of 37 of these markers was established. Importantly, five of them are expressed in DDK oocytes and are candidate genes for the maternal factor, and 20 are candidate genes for the paternal factor since they are expressed in testis. This data is an important step towards identifying the genes responsible for the DDK syndrome.

    Gene 2002;296;1-2;75-86

  • The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane.

    Gan Y, McGraw TE and Rodriguez-Boulan E

    Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021, USA.

    To perform vectorial secretory and transport functions that are critical for the survival of the organism, epithelial cells sort plasma membrane proteins into polarized apical and basolateral domains. Sorting occurs post-synthetically, in the trans Golgi network (TGN) or after internalization from the cell surface in recycling endosomes, and is mediated by apical and basolateral sorting signals embedded in the protein structure. Basolateral sorting signals include tyrosine motifs in the cytoplasmic domain that are structurally similar to signals involved in receptor internalization by clathrin-coated pits. Recently, an epithelial-specific adaptor protein complex, AP1B, was identified. AP-1B recognizes a subset of basolateral tyrosine motifs through its mu 1B subunit. Here, we characterized the post-synthetic and post-endocytic sorting of the fast recycling low density lipoprotein receptor (LDLR) and transferrin receptor (TfR) in LLC-PK1 cells, which lack mu 1B and mis-sort both receptors to the apical surface. Targeting and recycling assays in LLC-PK1 cells, before and after transfection with mu 1B, and in MDCK cells, which express mu 1B constitutively, suggest that AP1B sorts basolateral proteins post-endocytically.

    Funded by: NEI NIH HHS: EY08538, R01 EY008538; NIDDK NIH HHS: DK-52852, DK-57689; NIGMS NIH HHS: GM34107, R01 GM034107

    Nature cell biology 2002;4;8;605-9

  • Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.

    Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood WH, Becker KG and Ko MS

    Laboratory of Genetics and DNA Array Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6820, USA.

    cDNA microarray technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to mammalian development have been hampered by the lack of appropriate cDNA collections, particularly for early developmental stages. To overcome this problem, a PCR-based cDNA library construction method was used to derive 52,374 expressed sequence tags from pre- and peri-implantation embryos, embryonic day (E) 12.5 female gonad/mesonephros, and newborn ovary. From these cDNA collections, a microarray representing 15,264 unique genes (78% novel and 22% known) was assembled. In initial applications, the divergence of placental and embryonic gene expression profiles was assessed. At stage E12.5 of development, based on triplicate experiments, 720 genes (6.5%) displayed statistically significant differences in expression between placenta and embryo. Among 289 more highly expressed in placenta, 61 placenta-specific genes encoded, for example, a novel prolactin-like protein. The number of genes highly expressed (and frequently specific) for placenta has thereby been increased 5-fold over the total previously reported, illustrating the potential of the microarrays for tissue-specific gene discovery and analysis of mammalian developmental programs.

    Proceedings of the National Academy of Sciences of the United States of America 2000;97;16;9127-32

  • Identification and characterization of novel clathrin adaptor-related proteins.

    Takatsu H, Sakurai M, Shin HW, Murakami K and Nakayama K

    Institute of Biological Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.

    We have identified a human approximately 87-kDa protein, designated as gamma2-adaptin, that is similar to gamma-adaptin (called gamma1-adaptin in this paper), a large chain of the AP-1 clathrin-associated adaptor complex, not only in the primary structure (60% amino acid identity) but also in the domain organization. Northern blot analysis has shown that its mRNA is expressed in a variety of tissues. Analysis using a yeast two-hybrid system has revealed that, similarly to gamma1-adaptin, gamma2-adaptin is capable of interacting not only with the sigma1 chain (called as sigma1A in this paper), the small chain of the AP-1 complex, but also with a novel sigma1-like protein, designated as sigma1B, which shows an 87% amino acid identity to sigma1A; and that, unlike gamma1-adaptin, it is unable to interact with beta1-adaptin, another large chain of the AP-1 complex. Immunofluorescence microscopy analysis has revealed that gamma2-adaptin is localized to paranuclear vesicular structures that are not superimposed on structures containing gamma1-adaptin. Furthermore, unlike gamma1-adaptin, gamma2-adaptin is recruited onto membranes in the presence of a fungal antibiotic, brefeldin A. These data suggest that gamma2-adaptin constitute a novel adaptor-related complex that participates in a transport step different from that of AP-1.

    The Journal of biological chemistry 1998;273;38;24693-700

  • ATM binds to beta-adaptin in cytoplasmic vesicles.

    Lim DS, Kirsch DG, Canman CE, Ahn JH, Ziv Y, Newman LS, Darnell RB, Shiloh Y and Kastan MB

    Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.

    Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.

    Funded by: NCI NIH HHS: CA71387, R01 CA071387; NIGMS NIH HHS: GM07309, T32 GM007309

    Proceedings of the National Academy of Sciences of the United States of America 1998;95;17;10146-51

  • The AP-3 complex: a coat of many colours.

    Odorizzi G, Cowles CR and Emr SD

    Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093-0668, USA.

    A new adaptor protein complex, termed AP-3, has recently been identified in mammalian cells, and genetic studies in yeast have revealed a functional role for the AP-3 complex in cargo-selective transport via a new alternative trafficking pathway from the Golgi to the vacuole/lysosome. Here, the authors review what is currently known about the AP-3 complex and discuss recent insight into its function in multicellular organisms that has come from the finding that mutations in AP-3 subunits correspond to classical mutations in Drosophila and mice.

    Trends in cell biology 1998;8;7;282-8

  • Characterization of the human NIPSNAP1 gene from 22q12: a member of a novel gene family.

    Seroussi E, Pan HQ, Kedra D, Roe BA and Dumanski JP

    Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

    Rapid progress in sequencing of human and other genomes allows high-resolution analysis of their gene content on the basis of comparison between species. We have used a combined computer and biochemical approach to characterize 135 kb of human genomic sequence from 22q12 and discovered a new 10 exon gene, termed NIPSNAP1, located between the neurofibromatosis type 2 and the pK1.3 genes. The NIPSNAP1 gene spans 26 kb of genomic sequence and shows to large introns in the 5'-region. All exon-intron junctions contain the gt/ag consensus splice site. The putative promoter of the NIPSNAP1 gene is TATA-less and resides in a GC-rich island characteristic of housekeeping genes. The NIPSNAP1 mRNA is 2.1 kb, is expressed ubiquitously at variable levels, with the highest expression in liver, is terminated by an uncommon ATTAAA polyadenylation site, and is capable of encoding a 284-amino-acid protein. This NIPSNAP1 protein has a strong sequence similarity limited to the central portion of a hypothetical protein (acc. P34492) from chromosome III of C. elegans, in which the other portions resemble a 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein. Thus, the NIPSNAP1 gene is a member of an evolutionarily well conserved, novel gene family with two members in human and mouse that have now been characterized, and one member in C. elegans. The second human gene, NIPSNAP2, is localized in the vicinity of marker D7S499 on chromosome 7. Although the function of the NIPSNAP protein family is unknown, clues about its role may reside in the co-expression of the C. elegans orthologue, within an operon encoding protein motifs known to be involved in vesicular transport.

    Gene 1998;212;1;13-20

  • Characterization of the mouse beta-prime adaptin gene; cDNA sequence, genomic structure, and chromosomal localization.

    Guilbaud C, Peyrard M, Fransson I, Clifton SW, Roe BA, Carter NP and Dumanski JP

    Department of Molecular Medicine, Karolinska Hospital, CMM-building L8:00, S-171 76 Stockholm, Sweden.

    Adaptins are important subunits of heterotetrameric complexes called adaptors, which participate in the clathrin-coated, vesicle-mediated endocytosis and intracellular receptor transport. The gene family of adaptins is divided into three classes, alpha, beta, and gamma, with further subdivision into beta- and beta-prime components. Two beta-prime adaptins, the rat AP105a and the human BAM22, have previously been characterized. The BAM22 gene is located on human Chromosome (Chr) 22q12 and can be considered a candidate meningioma tumor suppressor gene. We report here the characterization of the mouse ortholog of the BAM22 gene, and we suggest the name adtb1 for the mouse gene. Like the BAM22 gene, the adtb1 transcript is highly and ubiquitously expressed. We provide 3885-bp cDNA sequence, which entirely covers the open reading frame of the adtb1, capable of encoding a protein of 943 amino acids. The adtb1 protein is highly conserved (>96% identity) when compared with AP105a and BAM22 proteins. We also report the genomic organization of adtb1, which is similar to the BAM22 gene. The adtb1 gene has been assigned to mouse Chr 11, band 11A2, which confirms the synteny between human Chr 22q12 and mouse Chr 11.

    Mammalian genome : official journal of the International Mammalian Genome Society 1997;8;9;651-6

Gene lists (8)

Gene List Source Species Name Description Gene count
L00000001 G2C Mus musculus Mouse PSD Mouse PSD adapted from Collins et al (2006) 1080
L00000003 G2C Mus musculus Mouse clathrin Mouse clathrin coated vesicle genes adapted from Collins et al (2006) 150
L00000004 G2C Mus musculus Mouse Synaptosome Mouse Synaptosome adapted from Collins et al (2006) 152
L00000008 G2C Mus musculus Mouse PSP Mouse PSP adapted from Collins et al (2006) 1121
L00000060 G2C Mus musculus BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus (ortho) 748
L00000062 G2C Mus musculus BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus 984
L00000070 G2C Mus musculus BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list (ortho) 1461
L00000072 G2C Mus musculus BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list 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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