Gene Symbol: Syn2
Description: synapsin II
Alias: 2900074L19Rik, AI836018, AI841723, synapsin-2
Species: mouse
Products:     Syn2

Top Publications

  1. Tollet J, Everett A, Sparrow M. Spatial and temporal distribution of nerves, ganglia, and smooth muscle during the early pseudoglandular stage of fetal mouse lung development. Dev Dyn. 2001;221:48-60 pubmed
    ..By using fluorescent markers and confocal microscopy, we present the developing lung as a dynamic structure with smooth muscle and neural tissue in a prime position to influence growth and development. ..
  2. 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. ..
  3. 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. ..
  4. 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
  5. 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. ..
  6. 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. ..
  7. Bogen I, Jensen V, Hvalby Ø, Walaas S. Glutamatergic neurotransmission in the synapsin I and II double knock-out mouse. Semin Cell Dev Biol. 2011;22:400-7 pubmed publisher
  8. 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. ..
  9. 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

More Information


  1. 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 results of the modelling were in a good agreement with the observed dependence of vesicle distribution on synapsin II and calcium deficiency. ..
  2. 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
  3. 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. ..
  4. Samigullin D, Bill C, Coleman W, Bykhovskaia M. Regulation of transmitter release by synapsin II in mouse motor terminals. J Physiol. 2004;561:149-58 pubmed
    ..Thus, at the reduced Ca(2+) concentration, synapsin II suppressed transmitter release and facilitation. These results demonstrate that synapsin II can regulate vesicle clustering, transmitter release, and facilitation. ..
  5. 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. ..
  6. 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
    ..LEV ameliorates such hyper excitability by enhancing the inhibition/excitation ratio, although the effect is hindered in TKO slices which exhibit a concomitant decrease in the levels of the LEV receptor SV2A. ..
  7. 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
  8. 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
  9. Medrihan L, Cesca F, Raimondi A, Lignani G, Baldelli P, Benfenati F. Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by interacting with presynaptic calcium channels. Nat Commun. 2013;4:1512 pubmed publisher
    ..Synapsin II (SYN2) is a member of the multigene synapsin family (SYN1/2/3) of synaptic vesicle phosphoproteins that modulate synaptic ..
  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. 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
    ..families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition...
  12. 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. ..
  13. Dyck B, Skoblenick K, Castellano J, Ki K, Thomas N, Mishra R. Behavioral abnormalities in synapsin II knockout mice implicate a causal factor in schizophrenia. Synapse. 2009;63:662-72 pubmed publisher
  14. 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
    ..All these changes preceded the appearance of epilepsy, indicating that the distinct changes in excitatory and inhibitory transmission due to the absence of Syns initiate the epileptogenic process. ..
  15. 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. ..
  16. 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+. ..
  17. 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. ..
  18. Feliciano P, Matos H, Andrade R, Bykhovskaia M. Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype. J Neurosci. 2017;37:1757-1771 pubmed publisher
    ..These results reveal a new SynII function in the regulation of the time course of GABA release and demonstrate that this function is dependent on the interneuron subtype. ..
  19. Skoblenick K, Argintaru N, Xu Y, Dyck B, Basu D, Tan M, et al. Role of AP-2alpha transcription factor in the regulation of synapsin II gene expression by dopamine D1 and D2 receptors. J Mol Neurosci. 2010;41:267-77 pubmed publisher
  20. Owe S, Erisir A, Heggelund P. Terminals of the major thalamic input to visual cortex are devoid of synapsin proteins. Neuroscience. 2013;243:115-25 pubmed publisher
    ..Furthermore, VGluT2 and synapsins were colocalized in other brain structures, suggesting that lack of synapsins is not a property of VGluT2-containing terminals, but a property of primary driver terminals in the visual system. ..
  21. 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. ..
  22. 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 II (synapsin 2 knock-out mice, Syn2KO mice) all seizures are in the form of generalized tonic-clonic seizures...
  23. Potts R, Zhang P, Wurster A, Precht P, Mughal M, Wood W, et al. CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes. PLoS ONE. 2011;6:e24515 pubmed publisher
    ..CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease. ..
  24. Gabriel T, Garcia Perez E, Mahfooz K, Goni J, Martínez Turrillas R, Pérez Otaño I, et al. A new kinetic framework for synaptic vesicle trafficking tested in synapsin knock-outs. J Neurosci. 2011;31:11563-77 pubmed publisher
  25. Frederikse P, Yun E, Kao H, Zigler J, Sun Q, Qazi A. Synapsin and synaptic vesicle protein expression during embryonic and post-natal lens fiber cell differentiation. Mol Vis. 2004;10:794-804 pubmed
  26. Naylor S, Carritt B, Boileau C, Beroud C, Alexander C, Allderdice P, et al. Report of the sixth international workshop on human chromosome 3 mapping 1995. Cytogenet Cell Genet. 1996;72:255-70 pubmed
  27. Ketzef M, Gitler D. Epileptic synapsin triple knockout mice exhibit progressive long-term aberrant plasticity in the entorhinal cortex. Cereb Cortex. 2014;24:996-1008 pubmed publisher
    ..In conclusion, although congenital impairments in inhibitory transmission may initiate epileptogenesis in the synapsin TKO mice, we suggest that secondary adaptations are crucial for the establishment of this epileptic network. ..
  28. 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
  29. Schmidtko A, Del Turco D, Coste O, Ehnert C, Niederberger E, Ruth P, et al. Essential role of the synaptic vesicle protein synapsin II in formalin-induced hyperalgesia and glutamate release in the spinal cord. Pain. 2005;115:171-81 pubmed
    ..The distinctive role of synapsin II for pain signaling probably results from its specific localization and possibly from a specific control of glutamate release. ..
  30. Rahkonen O, Koskivirta I, Oksjoki S, Jokinen E, Vuorio E. Characterization of the murine Timp4 gene, localization within intron 5 of the synapsin 2 gene and tissue distribution of the mRNA. Biochim Biophys Acta. 2002;1577:45-52 pubmed
    ..The gene is located on mouse chromosome 6 in an antisense orientation between exons 5 and 6 of the mouse synapsin 2 (Syn2) gene...
  31. Medrihan L, Ferrea E, Greco B, Baldelli P, Benfenati F. Asynchronous GABA Release Is a Key Determinant of Tonic Inhibition and Controls Neuronal Excitability: A Study in the Synapsin II-/- Mouse. Cereb Cortex. 2015;25:3356-68 pubmed publisher
  32. Chin L, Fu Q, Kachinsky A, Jabren G, Niu Y, Li L. Neuron-specific and developmental regulation of the synapsin II gene expression in transgenic mice. Brain Res Mol Brain Res. 1999;67:239-46 pubmed
    ..These results indicate that the 5.1-kb flanking sequence of the murine synapsin II gene contains cis-regulatory elements that are required for directing neuron-specific and synaptogenesis-regulated expression in vivo. ..
  33. Reinert R, Cai Q, Hong J, Plank J, Aamodt K, Prasad N, et al. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding. Development. 2014;141:1480-91 pubmed publisher
  34. 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. ..
  35. Kang S, Zhang M, Burgos M, Lubec G. Mass spectrometrical characterisation of mouse and rat synapsin isoforms 2a and 2b. Amino Acids. 2010;38:1131-43 pubmed publisher
    b>Synapsin 2 proteins are key elements of the synaptic machinery and still hold the centre stage in neuroscience research...
  36. Bogen I, Haug K, Roberg B, Fonnum F, Walaas S. The importance of synapsin I and II for neurotransmitter levels and vesicular storage in cholinergic, glutamatergic and GABAergic nerve terminals. Neurochem Int. 2009;55:13-21 pubmed publisher
    ..In conclusion, the results indicate that neurotransmitter regulation in central cholinergic synapses may be less dependent on synapsin I and II compared to the marked alterations seen in the glutamatergic and GABAergic synapses. ..
  37. 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. ..
  38. 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. ..
  39. LONART G, Simsek Duran F. Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation. Brain Res. 2006;1107:42-51 pubmed
  40. Cruceanu C, Alda M, Nagy C, Freemantle E, Rouleau G, Turecki G. H3K4 tri-methylation in synapsin genes leads to different expression patterns in bipolar disorder and major depression. Int J Neuropsychopharmacol. 2013;16:289-99 pubmed publisher
    The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 and SYN3) with alternative splicing resulting in a number of variants with various levels of homology...
  41. Bogen I, Risa Ø, Haug K, Sonnewald U, Fonnum F, Walaas S. Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles. J Neurochem. 2008;105:2524-34 pubmed publisher
  42. Li X, Rosahl T, Sudhof T, Francke U. Mapping of synapsin II (SYN2) genes to human chromosome 3p and mouse chromosome 6 band F. Cytogenet Cell Genet. 1995;71:301-5 pubmed
    ..While the gene for synapsin I (SYN1) is on the X chromosome, we have now assigned the human and mouse synapsin II (SYN2) genes to autosomes...
  43. Feliciano P, Andrade R, Bykhovskaia M. Synapsin II and Rab3a cooperate in the regulation of epileptic and synaptic activity in the CA1 region of the hippocampus. J Neurosci. 2013;33:18319-30 pubmed publisher
  44. Toader O, Forte N, Orlando M, Ferrea E, Raimondi A, Baldelli P, et al. Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures. Front Cell Neurosci. 2013;7:138 pubmed publisher
    ..Our data provide new insights into the mechanisms of epileptogenesis in the Syn II(-/-) mice and open the possibility for early diagnosis and therapeutic interventions. ..
  45. Shen Q, Wang X, Chen Y, Xu L, Wang X, Lu L. Expression QTL and regulatory network analysis of microtubule-associated protein tau gene. Parkinsonism Relat Disord. 2009;15:525-31 pubmed publisher
    ..These results demonstrate that the genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits, such as neurodegenerative disorders. ..
  46. Villanueva M, Thornley K, Augustine G, Wightman R. Synapsin II negatively regulates catecholamine release. Brain Cell Biol. 2006;35:125-36 pubmed
  47. Li L, Chin L, Greengard P, Copeland N, Gilbert D, Jenkins N. Localization of the synapsin II (SYN2) gene to human chromosome 3 and mouse chromosome 6. Genomics. 1995;28:365-6 pubmed
  48. Inoue D, Kimura I, Wakabayashi M, Tsumoto H, Ozawa K, Hara T, et al. Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. FEBS Lett. 2012;586:1547-54 pubmed publisher
    ..activation of sympathetic neurons by SCFA propionate involves SCFA receptor GPR41 linking to G??-PLC?3-ERK1/2-synapsin 2 signaling...
  49. 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
  50. Schmidtko A, Luo C, Gao W, Geisslinger G, Kuner R, Tegeder I. Genetic deletion of synapsin II reduces neuropathic pain due to reduced glutamate but increased GABA in the spinal cord dorsal horn. Pain. 2008;139:632-43 pubmed publisher
  51. 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. ..
  52. Oettinger H, Streeter H, Lose E, Copeland N, Gilbert D, Justice M, et al. Chromosome mapping of the murine syndecan gene. Genomics. 1991;11:334-8 pubmed
    ..The syndecan gene is likely on human Chromosome 2 because this region shows conservation of synteny between mouse and human chromosomes. ..
  53. 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. ..