Summary: A family of synaptic vesicle-associated proteins involved in the short-term regulation of NEUROTRANSMITTER release. Synapsin I, the predominant member of this family, links SYNAPTIC VESICLES to ACTIN FILAMENTS in the presynaptic nerve terminal. These interactions are modulated by the reversible PHOSPHORYLATION of synapsin I through various signal transduction pathways. The protein is also a substrate for cAMP- and CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. It is believed that these functional properties are also shared by synapsin II.

Top Publications

  1. Baldelli P, Fassio A, Corradi A, Cremona O, Valtorta F, Benfenati F. Synapsins and neuroexocytosis: recent views from functional studies on synapsin null mutant mice. Arch Ital Biol. 2005;143:113-26 pubmed
  2. Tao Cheng J, Dosemeci A, Winters C, Reese T. Changes in the distribution of calcium calmodulin-dependent protein kinase II at the presynaptic bouton after depolarization. Brain Cell Biol. 2006;35:117-24 pubmed
    ..Activity-induced redistribution of CaMKII leaves it in a position to facilitate phosphorylation of additional presynaptic proteins regulating neurotransmitter release. ..
  3. 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>Synapsins (Syn I, Syn II, and Syn III) are a family of synaptic vesicle phosphoproteins regulating synaptic transmission and plasticity...
  4. O Malley D, MacDonald N, Mizielinska S, Connolly C, Irving A, Harvey J. Leptin promotes rapid dynamic changes in hippocampal dendritic morphology. Mol Cell Neurosci. 2007;35:559-72 pubmed
  5. Siksou L, Rostaing P, Lechaire J, Boudier T, Ohtsuka T, Fejtova A, et al. Three-dimensional architecture of presynaptic terminal cytomatrix. J Neurosci. 2007;27:6868-77 pubmed
    ..This 3D analysis reveals the morphological constraints exerted by the presynaptic molecular scaffold. SVs are tightly interconnected in the axonal bouton, and this network is preferentially connected to the AZ. ..
  6. Porton B, Rodriguiz R, Phillips L, Gilbert J, Feng J, Greengard P, et al. Mice lacking synapsin III show abnormalities in explicit memory and conditioned fear. Genes Brain Behav. 2010;9:257-68 pubmed publisher
  7. 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. ..
  8. Chiappalone M, Casagrande S, Tedesco M, Valtorta F, Baldelli P, Martinoia S, et al. Opposite changes in glutamatergic and GABAergic transmission underlie the diffuse hyperexcitability of synapsin I-deficient cortical networks. Cereb Cortex. 2009;19:1422-39 pubmed publisher
    b>Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play a role in synaptic transmission and plasticity...
  9. Ekici M, Schmitz F, Hohl M, Seigel G, Thiel G. Chromatin structure and expression of synapsin I and synaptophysin in retinal precursor cells. Neurochem Int. 2008;53:165-72 pubmed publisher
    ..These data reveal that the synapsin I and synaptophysin genes are bona fide target genes for REST in R28 retinal precursor cells. ..

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  1. Harzsch S, Hansson B. Brain architecture in the terrestrial hermit crab Coenobita clypeatus (Anomura, Coenobitidae), a crustacean with a good aerial sense of smell. BMC Neurosci. 2008;9:58 pubmed publisher
  2. Gaffield M, Betz W. Synaptic vesicle mobility in mouse motor nerve terminals with and without synapsin. J Neurosci. 2007;27:13691-700 pubmed
    ..Thus, in TKO mice, and perhaps WT mice, a phospho-protein different from synapsin but otherwise of unknown identity is the primary regulator of synaptic vesicle mobility. ..
  3. Xue J, Liu Z, Hu J, Chen H, Zhang J, Chen N. Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway. Brain Res. 2006;1106:91-98 pubmed publisher
    ..b>Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release...
  4. Evergren E, Benfenati F, Shupliakov O. The synapsin cycle: a view from the synaptic endocytic zone. J Neurosci Res. 2007;85:2648-56 pubmed
    ..Recent studies have demonstrated that synapsins migrate to the endocytic zone of central synapses during neurotransmitter release, which suggests that there are ..
  5. Lachman H, Stopkova P, Papolos D, Pedrosa E, Margolis B, Aghalar M, et al. Analysis of synapsin III-196 promoter mutation in schizophrenia and bipolar disorder. Neuropsychobiology. 2006;53:57-62 pubmed
    ..EMSA showed that the region encompassing the -196 SNP binds to a brain protein in an allele-specific manner. These data, while inconclusive, suggest that -196 SNP should be further investigated as a candidate for 22q13-linked SZ. ..
  6. Khoutorsky A, Spira M. Activity-dependent calpain activation plays a critical role in synaptic facilitation and post-tetanic potentiation. Learn Mem. 2009;16:129-41 pubmed publisher
    ..The prevailing hypothesis assumes that synapsins play pivotal roles in these processes...
  7. Giachello C, Fiumara F, Giacomini C, Corradi A, Milanese C, Ghirardi M, et al. MAPK/Erk-dependent phosphorylation of synapsin mediates formation of functional synapses and short-term homosynaptic plasticity. J Cell Sci. 2010;123:881-93 pubmed publisher
  8. 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. ..
  9. 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. ..
  10. Lau B, Foldes A, Alieva N, Oliphint P, Busch D, Morgan J. Increased synapsin expression and neurite sprouting in lamprey brain after spinal cord injury. Exp Neurol. 2011;228:283-93 pubmed publisher
  11. 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
    ..The synapsins are a family of proteins that associate with synaptic vesicles and determine vesicle numbers at the terminal, ..
  12. Perlini L, Botti F, Fornasiero E, Giannandrea M, Bonanomi D, Amendola M, et al. Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I. J Cell Sci. 2011;124:3643-53 pubmed publisher
    b>Synapsins are synaptic vesicle (SV)-associated proteins that regulate synaptic transmission and neuronal differentiation...
  13. Chang Y, Tzeng S, Yu L, Huang A, Lee H, Huang C, et al. Early-life fluoxetine exposure reduced functional deficits after hypoxic-ischemia brain injury in rat pups. Neurobiol Dis. 2006;24:101-13 pubmed
    ..These findings suggest that functional deficits after HI in the developing brain can be reduced by agents that enhance neural plasticity and neurogenesis through CREB activation. ..
  14. Onofri F, Messa M, Matafora V, Bonanno G, Corradi A, Bachi A, et al. Synapsin phosphorylation by SRC tyrosine kinase enhances SRC activity in synaptic vesicles. J Biol Chem. 2007;282:15754-67 pubmed
    b>Synapsins are synaptic vesicle-associated phosphoproteins implicated in the regulation of neurotransmitter release. Synapsin I is the major binding protein for the SH3 domain of the kinase c-Src in synaptic vesicles...
  15. Jensen V, Walaas S, Hilfiker S, Ruiz A, Hvalby Ø. A delayed response enhancement during hippocampal presynaptic plasticity in mice. J Physiol. 2007;583:129-43 pubmed
    ..temperatures and essentially absent at 24 degrees C, was dependent on the presence of F-actin filaments and synapsins I and/or II, and could not be ascribed to changes in presynaptic action potentials, inhibitory neurotransmission ..
  16. 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. ..
  17. Dyck B, Tan M, Daya R, Basu D, Sookram C, Thomas N, et al. Behavioral effects of non-viral mediated RNA interference of synapsin II in the medial prefrontal cortex of the rat. Schizophr Res. 2012;137:32-8 pubmed publisher
  18. 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
    Several proteins in nerve terminals participate in synaptic transmission between neurons. The synapsins, which are synaptic vesicle-associated proteins, have widespread distribution in the brain and are assumed essential for sustained ..
  19. Fioravante D, Liu R, Netek A, Cleary L, Byrne J. Synapsin regulates Basal synaptic strength, synaptic depression, and serotonin-induced facilitation of sensorimotor synapses in Aplysia. J Neurophysiol. 2007;98:3568-80 pubmed
  20. Fiumara F, Milanese C, Corradi A, Giovedi S, Leitinger G, Menegon A, et al. Phosphorylation of synapsin domain A is required for post-tetanic potentiation. J Cell Sci. 2007;120:3228-37 pubmed
    ..The synapsins, a family of synaptic vesicle (SV)-associated phosphoproteins, have been implicated in PTP...
  21. 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
  22. Coleman W, Bill C, Simsek Duran F, LONART G, Samigullin D, Bykhovskaia M. Synapsin II and calcium regulate vesicle docking and the cross-talk between vesicle pools at the mouse motor terminals. J Physiol. 2008;586:4649-73 pubmed publisher
    The synapsins, an abundant and highly conserved family of proteins that associate with synaptic vesicles, have been implicated in regulating the synaptic vesicle cycle...
  23. 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
    b>Synapsins regulate synaptic transmission by controlling the reserve pool of synaptic vesicles. Each of the three mammalian synapsin genes is subject to alternative splicing, yielding several isoforms whose roles are unknown...
  24. Hvalby Ø, Jensen V, Kao H, Walaas S. Synapsin-regulated synaptic transmission from readily releasable synaptic vesicles in excitatory hippocampal synapses in mice. J Physiol. 2006;571:75-82 pubmed
    ..pool have been examined by comparing excitatory synaptic transmission in hippocampal slices from mice devoid of synapsins I and II and from wild-type control animals...
  25. Awizio A, Onofri F, Benfenati F, Bonaccurso E. Influence of synapsin I on synaptic vesicles: an analysis by force-volume mode of the atomic force microscope and dynamic light scattering. Biophys J. 2007;93:1051-60 pubmed
    ..A family of abundant extrinsic SV proteins, the synapsins, interact with SV proteins and phospholipids and play an important role in the regulation of SV trafficking and ..
  26. Wendt A, Speidel D, Danielsson A, Esguerra J, Bogen I, Walaas S, et al. Synapsins I and II are not required for insulin secretion from mouse pancreatic ?-cells. Endocrinology. 2012;153:2112-9 pubmed publisher
    b>Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic ?-cells has also been suggested to be regulated by synapsins...
  27. Fassio A, Raimondi A, Lignani G, Benfenati F, Baldelli P. Synapsins: from synapse to network hyperexcitability and epilepsy. Semin Cell Dev Biol. 2011;22:408-15 pubmed publisher
    ..b>Synapsins, although not essential for the basic development and functioning of neuronal networks, are extremely important ..
  28. Cesca F, Baldelli P, Valtorta F, Benfenati F. The synapsins: key actors of synapse function and plasticity. Prog Neurobiol. 2010;91:313-48 pubmed publisher
    The synapsins are a family of neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms...
  29. 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
    b>Synapsins (SynI, SynII, SynIII) are a multigene family of synaptic vesicle (SV) phosphoproteins implicated in the regulation of synaptic transmission and plasticity...
  30. Humeau Y, Candiani S, Ghirardi M, Poulain B, Montarolo P. Functional roles of synapsin: lessons from invertebrates. Semin Cell Dev Biol. 2011;22:425-33 pubmed publisher
    ..In this review, in light of insights got from invertebrate preparations, we discuss the role of synapsin in synaptogenesis and synaptic function, especially on short term plasticity. ..
  31. John J, Sunyer B, Hoger H, Pollak A, Lubec G. Hippocampal synapsin isoform levels are linked to spatial memory enhancement by SGS742. Hippocampus. 2009;19:731-8 pubmed publisher
    b>Synapsins are essential proteins for synaptic plasticity and there is no information available for their role in cognitive enhancement (CE) of spatial memory formation...
  32. Orenbuch A, Ayelet O, Shulman Y, Yoav S, Lipstein N, Noa L, et al. Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin. J Neurochem. 2012;120:248-58 pubmed publisher
    ..Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool...
  33. Dyck B, Skoblenick K, Castellano J, Ki K, Thomas N, Mishra R. Synapsin II knockout mice show sensorimotor gating and behavioural abnormalities similar to those in the phencyclidine-induced preclinical animal model of schizophrenia. Schizophr Res. 2007;97:292-3 pubmed
  34. Porton B, Wetsel W. Reduction of synapsin III in the prefrontal cortex of individuals with schizophrenia. Schizophr Res. 2007;94:366-70 pubmed
    ..These findings are consistent with growing evidence of presynaptic abnormalities and prefrontal cortical dysfunction in schizophrenia. ..
  35. Michels B, Diegelmann S, Tanimoto H, Schwenkert I, Buchner E, Gerber B. A role for Synapsin in associative learning: the Drosophila larva as a study case. Learn Mem. 2005;12:224-31 pubmed
    b>Synapsins are evolutionarily conserved, highly abundant vesicular phosphoproteins in presynaptic terminals...
  36. Bykhovskaia M. Synapsin regulation of vesicle organization and functional pools. Semin Cell Dev Biol. 2011;22:387-92 pubmed publisher
    ..Different synapsin isoforms have unique and non-redundant roles in the multifaceted synapsin function. ..
  37. Giachello C, Montarolo P, Ghirardi M. Synaptic functions of invertebrate varicosities: what molecular mechanisms lie beneath. Neural Plast. 2012;2012:670821 pubmed publisher
    ..In particular, the role of invertebrate synapsin in the formation of presynaptic terminals and the cell-to-cell interactions that induce specific structural and functional changes in their respective targets will be analyzed. ..
  38. Valtorta F, Pozzi D, Benfenati F, Fornasiero E. The synapsins: multitask modulators of neuronal development. Semin Cell Dev Biol. 2011;22:378-86 pubmed publisher
    ..b>Synapsins are a family of abundant neuronal phosphoproteins that have been extensively studied for their role in the ..
  39. Dagyte G, Luiten P, de Jager T, Gabriel C, Mocaer E, den Boer J, et al. Chronic stress and antidepressant agomelatine induce region-specific changes in synapsin I expression in the rat brain. J Neurosci Res. 2011;89:1646-57 pubmed publisher
    ..Moreover, agomelatine partially counteracts the stress effects on SynI, suggesting a modulation of synaptic function by this antidepressant. ..
  40. Fornasiero E, Bonanomi D, Benfenati F, Valtorta F. The role of synapsins in neuronal development. Cell Mol Life Sci. 2010;67:1383-96 pubmed publisher
    The synapsins, the first identified synaptic vesicle-specific proteins, are phosphorylated on multiple sites by a number of protein kinases and are involved in neurite outgrowth and synapse formation as well as in synaptic transmission...
  41. Monaldi I, Vassalli M, Bachi A, Giovedi S, Millo E, Valtorta F, et al. The highly conserved synapsin domain E mediates synapsin dimerization and phospholipid vesicle clustering. Biochem J. 2010;426:55-64 pubmed publisher
    b>Synapsins are abundant SV (synaptic vesicle)-associated phosphoproteins that regulate synapse formation and function...
  42. Wang Y, Yu L, Zhao T, Xu J, Liu Z, Liu Y, et al. No association between bipolar disorder and syngr1 or synapsin II polymorphisms in the Han Chinese population. Psychiatry Res. 2009;169:167-8 pubmed publisher
    ..A case-control study with these two genes was conducted in 506 bipolar disorder patients and 507 healthy individuals from the Han Chinese population. No association was found in this study. ..
  43. 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
    ..We therefore suggest that while deletion of the synapsins initially increases cortical network activity, this enhanced excitability is insufficient to elicit seizures...
  44. Coleman W, Bykhovskaia M. Cooperative regulation of neurotransmitter release by Rab3a and synapsin II. Mol Cell Neurosci. 2010;44:190-200 pubmed publisher
    ..Taken together, our results suggest that synapsin II and Rab3a have separate roles in maintaining the total store of synaptic vesicles and cooperate in promoting the latest steps of neuronal secretion. ..
  45. Wei H, Masterson S, Petry H, Bickford M. Diffuse and specific tectopulvinar terminals in the tree shrew: synapses, synapsins, and synaptic potentials. PLoS ONE. 2011;6:e23781 pubmed publisher
    ..We suggest that the convergent synaptic arrangements, as well as the unique synapsin content of tectopulvinar terminals, allow them to relay a dynamic range of visual signals from the SC. ..
  46. Kao H, Li P, Chao H, Janoschka S, Pham K, Feng J, et al. Early involvement of synapsin III in neural progenitor cell development in the adult hippocampus. J Comp Neurol. 2008;507:1860-70 pubmed publisher
    ..These findings suggest a distinct function for this synaptic vesicle protein, in addition to its role in neurotransmission. ..
  47. Saviouk V, Moreau M, Tereshchenko I, Brzustowicz L. Association of synapsin 2 with schizophrenia in families of Northern European ancestry. Schizophr Res. 2007;96:100-11 pubmed
    ..Review of the literature suggests that Syn2 is likely to be involved in the etiology or pathogenesis of schizophrenia. ..
  48. Sun J, Bronk P, Liu X, Han W, Sudhof T. Synapsins regulate use-dependent synaptic plasticity in the calyx of Held by a Ca2+/calmodulin-dependent pathway. Proc Natl Acad Sci U S A. 2006;103:2880-5 pubmed
    b>Synapsins are abundant synaptic-vesicle phosphoproteins that are known to regulate neurotransmitter release but whose precise function has been difficult to pinpoint...
  49. 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
    ..These results demonstrate that SYN1 is a novel predisposing gene to ASDs, in addition to epilepsy, and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases. ..
  50. Micheva K, Busse B, Weiler N, O Rourke N, Smith S. Single-synapse analysis of a diverse synapse population: proteomic imaging methods and markers. Neuron. 2010;68:639-53 pubmed publisher
    ..These results establish a means for the high-throughput acquisition of proteomic data from individual cortical synapses in situ. ..
  51. Velho T, Mello C. Synapsins are late activity-induced genes regulated by birdsong. J Neurosci. 2008;28:11871-82 pubmed publisher
    ..Here we show that the expression of several isoforms of synapsins, a group of phosphoproteins thought to regulate the dynamics of synaptic vesicle storage and release, is induced ..
  52. Fdez E, Hilfiker S. Vesicle pools and synapsins: new insights into old enigmas. Brain Cell Biol. 2006;35:107-15 pubmed
    b>Synapsins are a multigene family of neuron-specific phosphoproteins and comprise the most abundant synaptic vesicle proteins...
  53. 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. ..