G2Cdb::Gene report

Gene id
G00000009
Gene symbol
Syngap1 (MGI)
Species
Mus musculus
Description
synaptic Ras GTPase activating protein 1 homolog (rat)
Orthologue
G00000034 (Homo sapiens)

Databases (7)

Gene
ENSMUSG00000067629 (Ensembl mouse gene)
240057 (Entrez Gene)
18 (G2Cdb plasticity & disease)
Gene Expression
240057 (Genepaint)
Literature
603384 (OMIM)
Marker Symbol
MGI:3039785 (MGI)
Protein Sequence
XP_920298 (RefSeq peptide)

Synonyms (1)

  • Syngap

Alleles (3)

Allele Name Type Description Literature
A00000030 SYNGAP ko knockout Syngap1 (SynGAP) knockout  

Literature (15)

Pubmed - g2c

  • Synaptic Ras GTPase activating protein regulates pattern formation in the trigeminal system of mice.

    Barnett MW, Watson RF, Vitalis T, Porter K, Komiyama NH, Stoney PN, Gillingwater TH, Grant SG and Kind PC

    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.

    The development of ordered connections or "maps" within the nervous system is a common feature of sensory systems and is crucial for their normal function. NMDA receptors are known to play a key role in the formation of these maps; however, the intracellular signaling pathways that mediate the effects of glutamate are poorly understood. Here, we demonstrate that SynGAP, a synaptic Ras GTPase activating protein, is essential for the anatomical development of whisker-related patterns in the developing somatosensory pathways in rodent forebrain. Mice lacking SynGAP show only partial segregation of barreloids in the thalamus, and thalamocortical axons segregate into rows but do not form whisker-related patches. In cortex, layer 4 cells do not aggregate to form barrels. In Syngap(+/-) animals, barreloids develop normally, and thalamocortical afferents segregate in layer 4, but cell segregation is retarded. SynGAP is not necessary for the development of whisker-related patterns in the brainstem. Immunoelectron microscopy for SynGAP from layer 4 revealed a postsynaptic localization with labeling in developing postsynaptic densities (PSDs). Biochemically, SynGAP associates with the PSD in a PSD-95-independent manner, and Psd-95(-/-) animals develop normal barrels. These data demonstrate an essential role for SynGAP signaling in the activity-dependent development of whisker-related maps selectively in forebrain structures indicating that the intracellular pathways by which NMDA receptor activation mediates map formation differ between brain regions and developmental stage.

    Funded by: Medical Research Council: G0300466; Wellcome Trust

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26;5;1355-65

  • Differential expression of two NMDA receptor interacting proteins, PSD-95 and SynGAP during mouse development.

    Porter K, Komiyama NH, Vitalis T, Kind PC and Grant SG

    Centre for Neuroscience Research, University of Edinburgh, Edinburgh UK.

    Patterns of neural activity mediated by N-methyl-D-aspartate (NMDA) receptors are known to play important roles in development of the central nervous system. However, the signalling pathways downstream from NMDA receptors that are critical for normal neuronal development are not yet clearly understood. NMDA receptors interact with various signalling proteins via scaffolding proteins, which are important in adult neuronal and behavioural plasticity. For example, the NR2B subunits of the NMDA receptor interact with postsynaptic density 95 (PSD-95), which in turn binds to synaptic ras GTPase-activating protein (SynGAP). Interestingly, the developmental phenotype of mice carrying null mutations in these genes differ. NR2B and SynGAP homozygote mice die within the first week of birth whereas PSD-95 homozygote mice survive to adulthood. We therefore examined the expression patterns of PSD-95 and SynGAP genes from embryonic stages to adult using lacZ (beta-galactosidase) marker gene knock-in mice. Dramatic changes of expression were observed throughout development in brain and other tissues. Although SynGAP binds PSD-95, both genes had distinct, as well as overlapping expression. SynGAP expression peaked at times of synaptogenesis and developmental plasticity in contrast to PSD-95, which was expressed throughout the brain from early embryonic stages. Furthermore, SynGAP showed a more spatially restricted pattern as illustrated by its restriction to forebrain in contrast to PSD-95, which was also found in mid- and hindbrain. These data support the model that synaptic signalling complexes are heterogeneous and individual components show temporal and spatial specificity during development.

    The European journal of neuroscience 2005;21;2;351-62

  • SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor.

    Komiyama NH, Watabe AM, Carlisle HJ, Porter K, Charlesworth P, Monti J, Strathdee DJ, O'Carroll CM, Martin SJ, Morris RG, O'Dell TJ and Grant SG

    Division of Neuroscience, University of Edinburgh, Edinburgh EH8-9JZ, United Kingdom.

    At excitatory synapses, the postsynaptic scaffolding protein postsynaptic density 95 (PSD-95) couples NMDA receptors (NMDARs) to the Ras GTPase-activating protein SynGAP. The close association of SynGAP and NMDARs suggests that SynGAP may have an important role in NMDAR-dependent activation of Ras signaling pathways, such as the MAP kinase pathway, and in synaptic plasticity. To explore this issue, we examined long-term potentiation (LTP), p42 MAPK (ERK2) signaling, and spatial learning in mice with a heterozygous null mutation of the SynGAP gene (SynGAP(-/+)). In SynGAP(-/+) mutant mice, the induction of LTP in the hippocampal CA1 region was strongly reduced in the absence of any detectable alteration in basal synaptic transmission and NMDAR-mediated synaptic currents. Although basal levels of activated ERK2 were elevated in hippocampal extracts from SynGAP(-/+) mice, NMDAR stimulation still induced a robust increase in ERK activation in slices from SynGAP(-/+) mice. Thus, although SynGAP may regulate the ERK pathway, its role in LTP most likely involves additional downstream targets. Consistent with this, the amount of potentiation induced by stimulation protocols that induce an ERK-independent form of LTP were also significantly reduced in slices from SynGAP(-/+) mice. An elevation of basal phospho-ERK2 levels and LTP deficits were also observed in SynGAP(-/+)/H-Ras(-)/- double mutants, suggesting that SynGAP may normally regulate Ras isoforms other than H-Ras. A comparison of SynGAP and PSD-95 mutants suggests that PSD-95 couples NMDARs to multiple downstream signaling pathways with very different roles in LTP and learning.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2002;22;22;9721-32

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

  • Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

    Muhia M, Yee BK, Feldon J, Markopoulos F and Knuesel I

    Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology, Schwerzenbach, Switzerland.

    The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG(+/-) mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG(+/-) mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG(+/-) mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.

    The European journal of neuroscience 2010;31;3;529-43

  • Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice.

    Muhia M, Feldon J, Knuesel I and Yee BK

    Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology.

    The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG+/-) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition. When examined on differential reinforcement of low rates of response (DRL) schedules, SG+/- mice showed increased responding under DRL-4s and DRL-8s, without impairing the response efficiency (total rewards/total lever presses) because both rewarded and nonrewarded presses were elevated. Motivation was unaffected as evaluated using a progressive ratio (PR) schedule. Yet, SG+/- mice persisted in responding during extinction at the end of PR training, although an equivalent phenotype was not evident in extinction learning following FI-20s training. This extinction phenotype is therefore schedule-specific and cannot be generalized to Pavlovian conditioning. In conclusion, constitutive SynGAP reduction increases vigor in the execution of learned operant behavior without compromising its temporal control, yielding effects readily distinguishable from NMDAR blockade.

    Behavioral neuroscience 2009;123;5;1114-28

  • Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia.

    Guo X, Hamilton PJ, Reish NJ, Sweatt JD, Miller CA and Rumbaugh G

    Department of Neurobiology and Evelyn F. McKnight Brain Institute, The University of Alabama at Birmingham, Birmingham, AL 35294 , USA.

    Abnormal function of NMDA receptors is believed to be a contributing factor to the pathophysiology of schizophrenia. NMDAR subunits and postsynaptic-interacting proteins of these channels are abnormally expressed in some patients with this illness. In mice, reduced NMDAR expression leads to behaviors analogous to symptoms of schizophrenia, but reports of animals with mutations in core postsynaptic density proteins having similar a phenotype have yet to be reported. Here we show that reduced expression of the neuronal RasGAP and NMDAR-associated protein, SynGAP, results in abnormal behaviors strikingly similar to that reported in mice with reduced NMDAR function. SynGAP mutant mice exhibited nonhabituating and persistent hyperactivity that was ameliorated by the antipsychotic clozapine. An NMDAR antagonist, MK-801, induced hyperactivity in normal mice but SynGAP mutants were less responsive, suggesting that NMDAR hypofunction contributes to this behavioral abnormality. SynGAP mutants exhibited enhanced startle reactivity and impaired sensory-motor gating. These mice also displayed a complete lack of social memory and a propensity toward social isolation. Finally, SynGAP mutants had deficits in cued fear conditioning and working memory, indicating abnormal function of circuits that control emotion and choice. Our results demonstrate that SynGAP mutant mice have gross neurological deficits similar to other mouse models of schizophrenia. Because SynGAP interacts with NMDARs, and the signaling activity of this protein is regulated by these channels, our data in dicate that SynGAP lies downstream of NMDARs and is a required intermediate for normal neural circuit function and behavior. Taken together, these data support the idea that schizophrenia may arise from abnormal signaling pathways that are mediated by NMDA receptors.

    Funded by: NIDA NIH HHS: R00 DA024761; NINDS NIH HHS: R01 NS064079

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2009;34;7;1659-72

  • Age-related accumulation of Reelin in amyloid-like deposits.

    Knuesel I, Nyffeler M, Mormède C, Muhia M, Meyer U, Pietropaolo S, Yee BK, Pryce CR, LaFerla FM, Marighetto A and Feldon J

    Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. knuesel@pharma.uzh.ch

    Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits. These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Abeta species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD.

    Neurobiology of aging 2009;30;5;697-716

  • SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin.

    Carlisle HJ, Manzerra P, Marcora E and Kennedy MB

    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

    SynGAP, a prominent Ras/Rap GTPase-activating protein in the postsynaptic density, regulates the timing of spine formation and trafficking of glutamate receptors in cultured neurons. However, the molecular mechanisms by which it does this are unknown. Here, we show that synGAP is a key regulator of spine morphology in adult mice. Heterozygous deletion of synGAP was sufficient to cause an excess of mushroom spines in adult brains, indicating that synGAP is involved in steady-state regulation of actin in mature spines. Both Ras- and Rac-GTP levels were elevated in forebrains from adult synGAP(+/-) mice. Rac is a well known regulator of actin polymerization and spine morphology. The steady-state level of phosphorylation of cofilin was also elevated in synGAP(+/-) mice. Cofilin, an F-actin severing protein that is inactivated by phosphorylation, is a downstream target of a pathway regulated by Rac. We show that transient regulation of cofilin by treatment with NMDA is also disrupted in synGAP mutant neurons. Treatment of wild-type neurons with 25 mum NMDA triggered transient dephosphorylation and activation of cofilin within 15 s. In contrast, neurons cultured from mice with a homozygous or heterozygous deletion of synGAP lacked the transient regulation by the NMDA receptor. Depression of EPSPs induced by a similar treatment of hippocampal slices with NMDA was disrupted in slices from synGAP(+/-) mice. Our data show that synGAP mediates a rate-limiting step in steady-state regulation of spine morphology and in transient NMDA-receptor-dependent regulation of the spine cytoskeleton.

    Funded by: NINDS NIH HHS: F32 NS047894, F32NS47894, NS17660, R01 NS017660, R01 NS017660-23A2, R01 NS017660-24, R01 NS017660-25, R01 NS017660-26

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2008;28;50;13673-83

  • SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.

    Rumbaugh G, Adams JP, Kim JH and Huganir RL

    Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

    Silent synapses, or excitatory synapses that lack functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), are thought to be critical for regulation of neuronal circuits and synaptic plasticity. Here, we report that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse number, and excitatory synaptic transmission in hippocampal and cortical cultured neurons. Overexpression of SynGAP in neurons results in a remarkable depression of AMPAR-mediated miniature excitatory postsynaptic currents, a significant reduction in synaptic AMPAR surface expression, and a decrease in the insertion of AMPARs into the plasma membrane. This change is specific for AMPARs because no change is observed in synaptic NMDA receptor expression or total synapse density. In contrast to these results, synaptic transmission is increased in neurons from SynGAP knockout mice as well as in neuronal cultures treated with SynGAP small interfering RNA. In addition, activation of the extracellular signal-regulated kinase, ERK, is significantly decreased in SynGAP-overexpressing neurons, whereas P38 mitogen-activated protein kinase (MAPK) signaling is potentiated. Furthermore, ERK activation is up-regulated in neurons from SynGAP knockout mice, whereas P38 MAPK function is depressed. Taken together, these data suggest that SynGAP plays a critical role in the regulation of neuronal MAPK signaling, AMPAR membrane trafficking, and excitatory synaptic transmission.

    Funded by: NIMH NIH HHS: R01 MH 64856, R01 MH064856; NINDS NIH HHS: F32 NS 43071, F32 NS043071

    Proceedings of the National Academy of Sciences of the United States of America 2006;103;12;4344-51

  • A mutation in the Icsbp1 gene causes susceptibility to infection and a chronic myeloid leukemia-like syndrome in BXH-2 mice.

    Turcotte K, Gauthier S, Tuite A, Mullick A, Malo D and Gros P

    Department of Biochemistry, McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada.

    BXH-2 mice develop a fatal myeloid leukemia by a two-step mutagenic process. First, a BXH-2-specific recessive mutation causes a myeloproliferative syndrome. Second, retroviral insertions alter oncogenes or tumor suppressors, resulting in clonal expansion of leukemic cells. We have identified a recessive locus on chromosome 8 (Myls) that is responsible for myeloproliferation in BXH-2. This Myls interval has been narrowed down to 2 Mb and found to contain several positional candidates, including the interferon consensus sequence-binding protein 1 gene (Icsbp, also known as interferon regulatory factor 8 [IRF8]). We show that BXH-2 mice carry a mutation (915 C to T) resulting in an arginine-to-cysteine substitution at position 294 within the predicted IRF association domain of the protein. Although expression of Icsbp1 mRNA transcripts is normal in BXH-2 splenocytes, these cells are unable to produce interleukin 12 and interferon-gamma in response to activating stimuli, confirming that R294C behaves as a loss-of-function mutation. Myeloproliferation in BXH-2 mice is concomitant to increased susceptibility to Mycobacterium bovis (BCG) despite the presence of resistance alleles at the Nramp1 locus. These results suggest a two-step model for chronic myeloid leukemia in BXH-2, in which inactivation of Icsbp1 predisposes to myeloproliferation and immunodeficiency. This event is required for retroviral replication, and subsequent insertional mutagenesis that causes leukemia in BXH-2 mice.

    Funded by: Canadian Institutes of Health Research: 12038-3

    The Journal of experimental medicine 2005;201;6;881-90

  • A role for synGAP in regulating neuronal apoptosis.

    Knuesel I, Elliott A, Chen HJ, Mansuy IM and Kennedy MB

    Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.

    The brain-specific Ras/Rap GTPase-activating protein synGAP is a major component of the postsynaptic density at glutamatergic synapses. It is a target for phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II, which up-regulates its GTPase-activating activity. Thus, SynGAP may play an important role in coupling N-methyl-D-aspartate-type glutamate receptor activation to signaling pathways downstream of Ras or Rap. Homozygous deletion of synGAP is lethal within the first few days after birth. Therefore, to study the functions of synGAP, we used the cre/loxP recombination system to produce conditional mice mutants in which gradual loss of synGAP begins at approximately 1 week, and usually becomes maximal by 3 weeks, after birth. The resulting phenotypes fall into two groups. In a small group, the level of synGAP protein is reduced to 20-25% of wild type, and they die at 2-3 weeks of age. In a larger group, the levels remain higher than approximately 40% of wild type, and they survive and remain healthy. In all mutants, however, an abnormally high number of neurons in the hippocampus and cortex undergo apoptosis, as detected by caspase-3 activation. The effect is cell autonomous, occurring only in neuronal types in which the synGAP gene is eliminated. The level of caspase-3 activation in neurons correlates inversely with the level of synGAP protein measured at 2 and 8 weeks after birth, indicating that neuronal apoptosis is enhanced by reduction of synGAP. These data show that synGAP plays a role in regulation of the onset of apoptotic neuronal death.

    Funded by: NINDS NIH HHS: NS17660, NS28710, R01 NS017660, R01 NS017660-24, R01 NS017660-25, R01 NS017660-26

    The European journal of neuroscience 2005;21;3;611-21

  • SynGAP regulates spine formation.

    Vazquez LE, Chen HJ, Sokolova I, Knuesel I and Kennedy MB

    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

    SynGAP is a brain-specific ras GTPase-activating protein that is an abundant component of the signaling complex associated with the NMDA-type glutamate receptor. We generated mutant mice lacking synGAP to study its physiological role. Homozygous mutant mice die in the first few days after birth; however, neurons from mutant embryos can be maintained in culture. Here, we report that spine and synapse formation are accelerated in cultured mutant neurons, and the spines of mature mutant neurons are significantly larger than those of wild type. Clusters of PSD-95 and subunits of AMPA-type and NMDA-type glutamate receptors accumulate in spines of mutant neurons by day 10 in vitro, whereas in wild-type neurons they are still mostly located in dendritic shafts. The frequency and amplitude of miniature EPSCs are larger in mutant neurons at day 10 in vitro, confirming that they have more functional synapses. At day 21 in vitro, the spines of mutant neurons remain significantly larger than those of wild type. The mutant phenotype at day 10 in vitro can be rescued by introduction of recombinant wild-type synGAP on day 9. In contrast, introduction of mutant synGAP with a mutated GAP domain or lacking the terminal domain that binds to PSD-95 does not rescue the mutant phenotype, indicating that both domains play a role in control of spine formation. Thus, the GAP activity of synGAP and its association with PSD-95 are important for normal regulation of spine and synapse formation in hippocampal neurons.

    Funded by: NIMH NIH HHS: 1T32MH20069, MH49176; NINDS NIH HHS: NS17660, NS28710, R01 NS017660, R01 NS017660-23A2, R01 NS017660-24, R01 NS017660-25, R01 NS017660-26

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2004;24;40;8862-72

  • Role of Unc51.1 and its binding partners in CNS axon outgrowth.

    Tomoda T, Kim JH, Zhan C and Hatten ME

    Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021-6399, USA.

    Previous studies showed that the serine/threonine kinase Unc51.1 is one of the earliest genes in neuronal differentiation and is required for granule cell axon formation. To examine the mechanism of Unc51.1 regulation of axon extension, we have identified two direct binding partners. The first, SynGAP, a negative regulator of Ras, is expressed within axons and growth cones of developing granule cells. Overexpression of SynGAP blocks neurite outgrowth by a mechanism that involves Ras-like GTPase cascade. The second binding partner is a PDZ domain-containing scaffolding protein, Syntenin, that binds Rab5 GTPase, the activity of which is attenuated by SynGAP. Thus, our results demonstrate that the Unc51.1-containing protein complex governs axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.

    Funded by: NINDS NIH HHS: NS39991, R01 NS039991

    Genes & development 2004;18;5;541-58

  • The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity.

    Kim JH, Lee HK, Takamiya K and Huganir RL

    Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.

    Synaptic GTPase-activating protein (SynGAP) is a neuronal RasGAP (Ras GTPase-activating protein) that is selectively expressed in brain and highly enriched at excitatory synapses, where it negatively regulates Ras activity and its downstream signaling pathways. To investigate the physiological role of SynGAP in the brain, we have generated mutant mice lacking the SynGAP protein. These mice exhibit postnatal lethality, indicating that SynGAP plays a critical role during neuronal development. In addition, cell biological experiments show that neuronal cultures from mutant mice have more synaptic AMPA receptor clusters, suggesting that SynGAP regulates glutamate receptor synaptic targeting. Moreover, electrophysiological studies demonstrated that heterozygous mutant mice have a specific defect in hippocampal long-term potentiation (LTP). These studies show that the regulation of synaptic Ras signaling by SynGAP is important for proper neuronal development and glutamate receptor trafficking and is critical for the induction of LTP.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2003;23;4;1119-24

Gene lists (11)

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
L00000007 G2C Mus musculus Mouse NRC Mouse NRC adapted from Collins et al (2006) 186
L00000008 G2C Mus musculus Mouse PSP Mouse PSP adapted from Collins et al (2006) 1121
L00000019 G2C Mus musculus Pocklington M1 Cluster 1 (mouse) from Pocklington et al (2006) 21
L00000050 G2C Mus musculus TAP-PSD-95-CORE TAP-PSD-95 pull-down core list 120
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).

Cookies Policy | Terms and Conditions. This site is hosted by Edinburgh University and the Genes to Cognition Programme.