Gene Symbol: Syn1
Description: synapsin I
Alias: Syn-1, Syn1-S, synapsin-1, truncated synapsin 1-S
Species: mouse
Products:     Syn1

Top Publications

  1. Takei Y, Harada A, Takeda S, Kobayashi K, Terada S, Noda T, et al. Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system. J Cell Biol. 1995;131:1789-800 pubmed
    ..These results suggest significant contribution of synapsin I to the formation and maintenance of the presynaptic structure. ..
  2. Schoch S, Cibelli G, Thiel G. Neuron-specific gene expression of synapsin I. Major role of a negative regulatory mechanism. J Biol Chem. 1996;271:3317-23 pubmed
    ..From these data we conclude that neuron-specific expression of synapsin I is accomplished by a negative regulatory mechanism via the NRSF/REST binding motif. ..
  3. Boido D, Farisello P, Cesca F, Ferrea E, Valtorta F, Benfenati F, et al. Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam. Neuroscience. 2010;171:268-83 pubmed publisher
    ..Synapsin I, II, I/II and I/II/III knockout mice are epileptic and SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans...
  4. Chin L, Li L, Ferreira A, Kosik K, Greengard P. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci U S A. 1995;92:9230-4 pubmed
    ..Furthermore, synapse formation was significantly delayed in these mutant neurons. These results indicate that synapsin I plays a role in regulation of axonogenesis and synaptogenesis. ..
  5. Etholm L, Heggelund P. Seizure elements and seizure element transitions during tonic-clonic seizure activity in the synapsin I/II double knockout mouse: a neuroethological description. Epilepsy Behav. 2009;14:582-90 pubmed publisher
    ..These differences may point to neurobiological mechanisms relevant to both rodent and human epilepsies. ..
  6. Gitler D, Cheng Q, Greengard P, Augustine G. Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles. J Neurosci. 2008;28:10835-43 pubmed publisher
  7. Bogen I, Boulland J, Mariussen E, Wright M, Fonnum F, Kao H, et al. Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters. J Neurochem. 2006;96:1458-66 pubmed
    ..In conclusion, distinct vesicular transporters show a variable degree of colocalization with synapsin proteins and, hence, distinct sensitivities to inactivation of the genes encoding synapsin I and II. ..
  8. Spillane D, Rosahl T, Sudhof T, Malenka R. Long-term potentiation in mice lacking synapsins. Neuropharmacology. 1995;34:1573-9 pubmed
    ..Although disappointing, these results are important in that they exclude the most abundant family of synaptic phosphoproteins as an essential component of long-term synaptic plasticity. ..
  9. Ryan T, Li L, Chin L, Greengard P, Smith S. Synaptic vesicle recycling in synapsin I knock-out mice. J Cell Biol. 1996;134:1219-27 pubmed

More Information


  1. Silva A, Rosahl T, Chapman P, Marowitz Z, Friedman E, Frankland P, et al. Impaired learning in mice with abnormal short-lived plasticity. Curr Biol. 1996;6:1509-18 pubmed
    ..Importantly, analysis of the SyI-/- mutants demonstrated that an increase in PPF does not disrupt learning. ..
  2. Kushner S, Elgersma Y, Murphy G, Jaarsma D, van Woerden G, Hojjati M, et al. Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway. J Neurosci. 2005;25:9721-34 pubmed
    ..Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory. ..
  3. Orenbuch A, Shalev L, Marra V, Sinai I, Lavy Y, Kahn J, et al. Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals. J Neurosci. 2012;32:3969-80 pubmed publisher
    ..Together, our results show that synapsin is pivotal for maintaining synaptic vesicle cluster integrity and that it contributes to the regulated sharing of vesicles between terminals. ..
  4. Fornasiero E, Raimondi A, Guarnieri F, Orlando M, Fesce R, Benfenati F, et al. Synapsins contribute to the dynamic spatial organization of synaptic vesicles in an activity-dependent manner. J Neurosci. 2012;32:12214-27 pubmed publisher
  5. Farisello P, Boido D, Nieus T, Medrihan L, Cesca F, Valtorta F, et al. Synaptic and extrasynaptic origin of the excitation/inhibition imbalance in the hippocampus of synapsin I/II/III knockout mice. Cereb Cortex. 2013;23:581-93 pubmed publisher
    ..b>SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans and synapsin I/II/III triple knockout ..
  6. Gitler D, Takagishi Y, Feng J, Ren Y, Rodriguiz R, Wetsel W, et al. Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J Neurosci. 2004;24:11368-80 pubmed
    ..Thus, synapsins maintain the reserve pool of glutamatergic vesicles but regulate the size of the readily releasable pool of GABAergic vesicles. ..
  7. Murrey H, Gama C, Kalovidouris S, Luo W, Driggers E, Porton B, et al. Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons. Proc Natl Acad Sci U S A. 2006;103:21-6 pubmed
    ..Together, our studies identify important roles for Fucalpha(1-2)Gal sugars in the regulation of neuronal proteins and morphological changes that may underlie synaptic plasticity. ..
  8. Fassio A, Patry L, Congia S, Onofri F, Piton A, Gauthier J, et al. SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function. Hum Mol Genet. 2011;20:2297-307 pubmed publisher
    ..Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of ..
  9. Shiina N, Yamaguchi K, Tokunaga M. RNG105 deficiency impairs the dendritic localization of mRNAs for Na+/K+ ATPase subunit isoforms and leads to the degeneration of neuronal networks. J Neurosci. 2010;30:12816-30 pubmed publisher
    ..The present study first demonstrates the in vivo role of RNG105 in the dendritic localization of mRNAs and uncovers a novel link between dendritic mRNA localization and the development and maintenance of functional networks. ..
  10. Rosahl T, Spillane D, Missler M, Herz J, Selig D, Wolff J, et al. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature. 1995;375:488-93 pubmed
  11. Cambiaghi M, Cursi M, Monzani E, Benfenati F, Comi G, Minicucci F, et al. Temporal evolution of neurophysiological and behavioral features of synapsin I/II/III triple knock-out mice. Epilepsy Res. 2013;103:153-60 pubmed publisher
    ..This aspect might be connected to brain dysfunction often associated to epilepsy in the interictal period. ..
  12. Kielland A, Erisir A, Walaas S, Heggelund P. Synapsin utilization differs among functional classes of synapses on thalamocortical cells. J Neurosci. 2006;26:5786-93 pubmed
    ..Together, this indicates that synapsin I and II are not present in the retinogeniculate terminals and therefore are not essential for sustained, high-rate synaptic transmission. ..
  13. Bogen I, Jensen V, Hvalby O, Walaas S. Synapsin-dependent development of glutamatergic synaptic vesicles and presynaptic plasticity in postnatal mouse brain. Neuroscience. 2009;158:231-41 pubmed publisher
  14. Thiel G, Schoch S, Petersohn D. Regulation of synapsin I gene expression by the zinc finger transcription factor zif268/egr-1. J Biol Chem. 1994;269:15294-301 pubmed
    ..From this data we conclude that the synapsin I gene is a target of the zif268 transcription factor; however, intermediate factors may also be involved in the activation. ..
  15. Hosaka M, Sudhof T. Synapsins I and II are ATP-binding proteins with differential Ca2+ regulation. J Biol Chem. 1998;273:1425-9 pubmed
    ..Our studies suggest that synapsins I and II function on synaptic vesicles as ATP-binding proteins that are differentially regulated by Ca2+. ..
  16. Ferreira A, Chin L, Li L, Lanier L, Kosik K, Greengard P. Distinct roles of synapsin I and synapsin II during neuronal development. Mol Med. 1998;4:22-8 pubmed
    ..Remarkably, the deletion of both synapsins led to partial restoration of the wild phenotype. The results suggest that the synapsins play separate but coordinated developmental roles. ..
  17. Gitler D, Xu Y, Kao H, Lin D, Lim S, Feng J, et al. Molecular determinants of synapsin targeting to presynaptic terminals. J Neurosci. 2004;24:3711-20 pubmed
    ..Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals. ..
  18. Hurley S, Brown D, Cheetham J. Cytoskeletal interactions of synapsin I in non-neuronal cells. Biochem Biophys Res Commun. 2004;317:16-23 pubmed
    ..These results demonstrate that synapsin I interacts with F-actin in non-neuronal cells and suggest that synapsin I may have a role in regions where actin is highly dynamic. ..
  19. Valente P, Casagrande S, Nieus T, Verstegen A, Valtorta F, Benfenati F, et al. Site-specific synapsin I phosphorylation participates in the expression of post-tetanic potentiation and its enhancement by BDNF. J Neurosci. 2012;32:5868-79 pubmed publisher
  20. Vosseller K, Trinidad J, Chalkley R, Specht C, Thalhammer A, Lynn A, et al. O-linked N-acetylglucosamine proteomics of postsynaptic density preparations using lectin weak affinity chromatography and mass spectrometry. Mol Cell Proteomics. 2006;5:923-34 pubmed
  21. Rosahl T, Geppert M, Spillane D, Herz J, Hammer R, Malenka R, et al. Short-term synaptic plasticity is altered in mice lacking synapsin I. Cell. 1993;75:661-70 pubmed
    ..In addition to potential redundant functions shared with other proteins, synapsin I in normal mice may function to limit increases in neurotransmitter release elicited by residual Ca2+ after an initial stimulus. ..
  22. Ketzef M, Kahn J, Weissberg I, Becker A, Friedman A, Gitler D. Compensatory network alterations upon onset of epilepsy in synapsin triple knock-out mice. Neuroscience. 2011;189:108-22 pubmed publisher
  23. Li L, Chin L, Shupliakov O, Brodin L, Sihra T, Hvalby O, et al. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci U S A. 1995;92:9235-9 pubmed
    ..These results provide strong support for the hypothesis that synapsin I plays a key role in the regulation of nerve terminal function in mature synapses. ..
  24. Etholm L, Linden H, Eken T, Heggelund P. Electroencephalographic characterization of seizure activity in the synapsin I/II double knockout mouse. Brain Res. 2011;1383:270-88 pubmed publisher
    ..Our findings suggest that seizure behavior in SynDKO mice is not solely determined by cortical activity but rather reflects interplay between cortical activity and activity in other brain regions. ..
  25. Corradi A, Zanardi A, Giacomini C, Onofri F, Valtorta F, Zoli M, et al. Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment. J Cell Sci. 2008;121:3042-51 pubmed publisher
    ..The data indicate that SynI and SynII have specific and non-redundant functions, and that synaptic dysfunctions associated with synapsin mutations negatively modulate cognitive performances and neuronal survival during senescence. ..
  26. Chi P, Greengard P, Ryan T. Synapsin dispersion and reclustering during synaptic activity. Nat Neurosci. 2001;4:1187-93 pubmed
    ..Thus synapsin acts as a phosphorylation-state-dependent regulator of synaptic vesicle mobilization, and hence, neurotransmitter release. ..
  27. Baldelli P, Fassio A, Valtorta F, Benfenati F. Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. J Neurosci. 2007;27:13520-31 pubmed
    ..We have studied the effects of the genetic ablation of the SYN1 gene on inhibitory synaptic transmission in primary hippocampal neurons...
  28. Terada S, Tsujimoto T, Takei Y, Takahashi T, Hirokawa N. Impairment of inhibitory synaptic transmission in mice lacking synapsin I. J Cell Biol. 1999;145:1039-48 pubmed
    ..This may explain, at least in part, the epileptic seizures occurring in the synapsin I mutant mice. ..
  29. Etholm L, Bahonjic E, Walaas S, Kao H, Heggelund P. Neuroethologically delineated differences in the seizure behavior of synapsin 1 and synapsin 2 knock-out mice. Epilepsy Res. 2012;99:252-9 pubmed publisher
    ..Through so called neuroethologically based analyses of fully established seizure behavior in Synapsin 1 and 2 knock-out mice (Syn1KO and Syn2KO mice) aged 4 1/2 months, this study reveals significant differences in ..
  30. Hosaka M, Sudhof T. Homo- and heterodimerization of synapsins. J Biol Chem. 1999;274:16747-53 pubmed
    ..The data also imply that synapsin III does not compensate for the loss of synapsins I and II in the double knockout mice. ..
  31. Maiya R, Ponomarev I, Linse K, Harris R, Mayfield R. Defining the dopamine transporter proteome by convergent biochemical and in silico analyses. Genes Brain Behav. 2007;6:97-106 pubmed
    ..In summary, this study identified a network of proteins that are primary candidates for functional regulation of the DAT, an important player in mechanisms of mental disorders and drug addiction. ..
  32. Etholm L, Bahonjic E, Heggelund P. Sensitive and critical periods in the development of handling induced seizures in mice lacking synapsins: differences between synapsin I and synapsin II knockouts. Exp Neurol. 2013;247:59-65 pubmed publisher
    ..In mice lacking synapsin I (synapsin 1 knock-out mice, Syn1KO mice) such seizures can either consist of mild myoclonic jerks or of fully developed ..
  33. Hippenmeyer S, Huber R, Ladle D, Murphy K, Arber S. ETS transcription factor Erm controls subsynaptic gene expression in skeletal muscles. Neuron. 2007;55:726-40 pubmed
    ..Together, our findings define Erm as an upstream regulator of a transcriptional program selective to subsynaptic nuclei at the NMJ and underscore the importance of transcriptional control of local synaptic protein accumulation. ..
  34. Gylterud Owe S, Bogen I, Walaas S, Storm Mathisen J, Bergersen L. Ultrastructural quantification of glutamate receptors at excitatory synapses in hippocampus of synapsin I+II double knock-out mice. Neuroscience. 2005;136:769-77 pubmed
  35. Jaffrey S, Benfenati F, Snowman A, Czernik A, Snyder S. Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON. Proc Natl Acad Sci U S A. 2002;99:3199-204 pubmed
    ..These results suggest a mechanism for specific actions of NO at presynaptic sites. ..
  36. Mullins L, Stephenson D, Grant S, Chapman V. Efficient linkage of 10 loci in the proximal region of the mouse X chromosome. Genomics. 1990;7:19-30 pubmed
    ..The possible significance of the Xlr loci is discussed with respect to other X-chromosome loci that regulate the immune response. ..
  37. Tu Y, Nayak S, Woodson J, Ross E. Phosphorylation-regulated inhibition of the Gz GTPase-activating protein activity of RGS proteins by synapsin I. J Biol Chem. 2003;278:52273-81 pubmed
    ..Synapsin can thus act as a phosphorylation-modulated mediator of feedback regulation of Gz signaling by the synaptic machinery. ..
  38. Lin Y, Wang H, Huang D, Hsieh P, Lin M, Chou C, et al. Neuronal Splicing Regulator RBFOX3 (NeuN) Regulates Adult Hippocampal Neurogenesis and Synaptogenesis. PLoS ONE. 2016;11:e0164164 pubmed publisher
    ..In addition, abnormalities in synaptic structure and function occur in Rbfox3 homozygous knockout mice. Our findings may offer mechanistic explanations for human brain diseases associated with dysfunctional RBFOX3. ..
  39. Yang Feng T, DeGennaro L, Francke U. Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci U S A. 1986;83:8679-83 pubmed
    ..We hypothesize that the synapsin I gene could be mutated in human X-linked disorders with primary neuronal degeneration, such as the Rett syndrome. ..
  40. Revest J, Kaouane N, Mondin M, le Roux A, Roug Pont F, Vall e M, et al. The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib. Mol Psychiatry. 2010;15:1125, 1140-51 pubmed publisher
  41. Venton B, Seipel A, Phillips P, Wetsel W, Gitler D, Greengard P, et al. Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool. J Neurosci. 2006;26:3206-9 pubmed
    ..This capacity to enhance exocytotic release of dopamine may be important for the psychostimulant actions of cocaine. ..
  42. Monea S, Jordan B, Srivastava S, DeSouza S, Ziff E. Membrane localization of membrane type 5 matrix metalloproteinase by AMPA receptor binding protein and cleavage of cadherins. J Neurosci. 2006;26:2300-12 pubmed
  43. Fogarty M, Smallcombe K, Yanagawa Y, Obata K, Bellingham M, Noakes P. Genetic deficiency of GABA differentially regulates respiratory and non-respiratory motor neuron development. PLoS ONE. 2013;8:e56257 pubmed publisher
    ..Our results also suggest that for more caudal (lumbar) regions of the spinal cord, the effect of GABA is less influential on motor neuron development compared to that of glycine. ..
  44. Greco B, Managò F, Tucci V, Kao H, Valtorta F, Benfenati F. Autism-related behavioral abnormalities in synapsin knockout mice. Behav Brain Res. 2013;251:65-74 pubmed publisher
    ..Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and ..
  45. Giannandrea M, Guarnieri F, Gehring N, Monzani E, Benfenati F, Kulozik A, et al. Nonsense-mediated mRNA decay and loss-of-function of the protein underlie the X-linked epilepsy associated with the W356× mutation in synapsin I. PLoS ONE. 2013;8:e67724 pubmed publisher
    ..Synapsin knock-out (Syn1(-/-) ) mice display an epileptic phenotype and mutations in the SYN1 gene have been identified in individuals ..
  46. Tanabe Y, Naito Y, Vasuta C, Lee A, Soumounou Y, Linhoff M, et al. IgSF21 promotes differentiation of inhibitory synapses via binding to neurexin2?. Nat Commun. 2017;8:408 pubmed publisher
    ..Here the authors show that IgSF21 interacts with neurexin2? to induce presynaptic differentiation of inhibitory synapses, and that mice lacking IgSF21 exhibit deficits in inhibitory synaptic transmission. ..
  47. Tan G, Liu Y, Wang L, Li K, Zhang Z, Li H, et al. PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res. 2018;28:90-110 pubmed publisher
    ..Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors. ..
  48. Medrihan L, Rohlmann A, Fairless R, Andrae J, Döring M, Missler M, et al. Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses. J Physiol. 2009;587:5095-106 pubmed publisher
  49. Kao H, Porton B, Hilfiker S, Stefani G, Pieribone V, DeSalle R, et al. Molecular evolution of the synapsin gene family. J Exp Zool. 1999;285:360-77 pubmed
    ..This was accompanied by the emergence of an additional conserved domain, termed A. J. Exp. Zool. ( Mol. Dev. Evol. ) 285:360-377, 1999. ..
  50. Lin T, Lu C, Wang C, Lu J, Wang S. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals. Toxicol Appl Pharmacol. 2012;263:233-43 pubmed publisher
    ..These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca²? entry and ERK/synapsin I signaling pathway. ..
  51. Baudet C, Pozas E, Adameyko I, Andersson E, Ericson J, Ernfors P. Retrograde signaling onto Ret during motor nerve terminal maturation. J Neurosci. 2008;28:963-75 pubmed publisher
    ..Thus, Ret transmits a signal in motor nerve terminals that participate in the organization and maturation of presynaptic specializations during development and during regeneration in the adult. ..
  52. Newman L, McKeever M, Okano H, Darnell R. Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle coat protein. Cell. 1995;82:773-83 pubmed
    ..We propose a model in which beta-NAP mediates vesicle transport between the soma and the axon terminus and suggest that beta-NAP may represent a general class of coat proteins that mediates apical transport in polarized cells. ..
  53. Mitchell M, Simon D, Affara N, Ferguson Smith M, Avner P, Bishop C. Localization of murine X and autosomal sequences homologous to the human Y located testis-determining region. Genetics. 1989;121:803-9 pubmed
    ..Comparative mapping indicates that in man these genes lie in separate conserved DNA segments. ..