Gene Symbol: Syt2
Description: synaptotagmin II
Alias: IP4BP, R74640, mKIAA4194, sytII, synaptotagmin-2, IP4-binding protein, inositol polyphosphate-binding protein
Species: mouse
Products:     Syt2

Top Publications

  1. Peng L, Berntsson R, Tepp W, Pitkin R, Johnson E, Stenmark P, et al. Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins. J Cell Sci. 2012;125:3233-42 pubmed publisher
    ..The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its ..
  2. Dong M, Richards D, Goodnough M, Tepp W, Johnson E, Chapman E. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J Cell Biol. 2003;162:1293-303 pubmed
    ..Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT/B. ..
  3. Nagy G, Kim J, Pang Z, Matti U, Rettig J, Sudhof T, et al. Different effects on fast exocytosis induced by synaptotagmin 1 and 2 isoforms and abundance but not by phosphorylation. J Neurosci. 2006;26:632-43 pubmed
    ..protein family, of which synaptotagmin 1 (Syt1) is a Ca2+ sensor for fast exocytosis, and its close relative, synaptotagmin 2 (Syt2), is assumed to serve similar functions. Chromaffin cells express Syt1 but not Syt2...
  4. Liu Y, Oppenheim R, Sugiura Y, Lin W. Abnormal development of the neuromuscular junction in Nedd4-deficient mice. Dev Biol. 2009;330:153-66 pubmed publisher
    ..Together, these results demonstrate that Nedd4 is involved in regulating the formation and function of the NMJs through non-cell autonomous mechanisms. ..
  5. Liu Y, Padgett D, Takahashi M, Li H, Sayeed A, Teichert R, et al. Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development. 2008;135:1957-67 pubmed publisher
    ..These results demonstrate that the gamma-subunit is required for the formation of pre-patterned AChR clusters, which in turn play an essential role in determining the subsequent pattern of neuromuscular synaptogenesis. ..
  6. Sun J, Pang Z, Qin D, Fahim A, Adachi R, Sudhof T. A dual-Ca2+-sensor model for neurotransmitter release in a central synapse. Nature. 2007;450:676-82 pubmed
    ..We show that deletion of synaptotagmin 2 (Syt2) in mice selectively abolishes synchronous release, allowing us to study pure asynchronous release in ..
  7. Pang Z, Melicoff E, Padgett D, Liu Y, Teich A, Dickey B, et al. Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses. J Neurosci. 2006;26:13493-504 pubmed
    ..Thus, synaptotagmin-2 is an essential synaptotagmin isoform that functions in concert with other synaptotagmins in the Ca2+ triggering of neurotransmitter release. ..
  8. Craxton M. Genomic analysis of synaptotagmin genes. Genomics. 2001;77:43-9 pubmed
    ..Comparison of the genomic structures of the Syt genes makes clear the different phylogenies of the different subgroups. Knowledge of the genomic structures will aid the systematic investigation of alternative splicing in Syt genes. ..
  9. Fox M, Sanes J. Synaptotagmin I and II are present in distinct subsets of central synapses. J Comp Neurol. 2007;503:280-96 pubmed
    ..The cell-, temporal-, and species-specific expression of synaptotagmin isoforms suggests that each may have distinct functions in neurotransmitter release. ..

More Information


  1. Rummel A, Karnath T, Henke T, Bigalke H, Binz T. Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G. J Biol Chem. 2004;279:30865-70 pubmed
    ..In addition, we show that the carboxyl-terminal domain of the cell binding fragment of BoNT/B and BoNT/G mediates the interaction with their protein receptor. ..
  2. Pang Z, Sun J, Rizo J, Maximov A, Sudhof T. Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. EMBO J. 2006;25:2039-50 pubmed
    b>Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function...
  3. Rummel A, Eichner T, Weil T, Karnath T, Gutcaits A, Mahrhold S, et al. Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept. Proc Natl Acad Sci U S A. 2007;104:359-64 pubmed
    ..The molecular characterization of the synaptotagmin binding site provides the basis for designing a novel class of potent binding inhibitors. ..
  4. Gautam M, Noakes P, Moscoso L, Rupp F, Scheller R, Merlie J, et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996;85:525-35 pubmed
  5. Chai Q, Arndt J, Dong M, Tepp W, Johnson E, Chapman E, et al. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature. 2006;444:1096-100 pubmed
    ..The results provide structural insights into how BoNTs recognize protein receptors and reveal a promising target for blocking toxin-receptor recognition. ..
  6. Chen F, Liu Y, Sugiura Y, Allen P, Gregg R, Lin W. Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors. Nat Neurosci. 2011;14:570-7 pubmed publisher
    ..Our findings indicate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ. ..
  7. Willison K. The mouse Brachyury gene and mesoderm formation. Trends Genet. 1990;6:104-5 pubmed
  8. Gundersen C, Umbach J. Synaptotagmins 1 and 2 as mediators of rapid exocytosis at nerve terminals: the dyad hypothesis. J Theor Biol. 2013;332:149-60 pubmed publisher
    ..The relative simplicity of this model and its amenability to empirical testing provide a useful template for future investigations of the molecular events underlying the exocytotic cascade. ..
  9. Morita T, Kubota H, Murata K, Nozaki M, Delarbre C, Willison K, et al. Evolution of the mouse t haplotype: recent and worldwide introgression to Mus musculus. Proc Natl Acad Sci U S A. 1992;89:6851-5 pubmed
    ..Hence, polymorphisms among t haplotypes including lethality factors have accumulated during this short time period independently in each M. musculus subspecies. ..
  10. Hilbush B, Morgan J. A third synaptotagmin gene, Syt3, in the mouse. Proc Natl Acad Sci U S A. 1994;91:8195-9 pubmed
    ..In the most highly conserved C2 domain, the mammalian synaptotagmins, SYT1 and SYT2, share 88% sequence identity, whereas SYT3 has only approximately 45% identity to either...
  11. Kwon O, Adamson M, Chin H, Kozak C. Genetic mapping of five mouse genes encoding synaptotagmins. Mamm Genome. 1995;6:880-1 pubmed
  12. Star E, Zhu M, Shi Z, Liu H, Pashmforoush M, Sauve Y, et al. Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6. Development. 2012;139:4644-55 pubmed publisher
    ..This work provides insight into the generation of neuronal subtypes by revealing a mechanism in which opposing, yet interdependent, transcription factors regulate subtype identity. ..
  13. Matsuoka R, Chivatakarn O, Badea T, SAMUELS I, Cahill H, Katayama K, et al. Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function. Neuron. 2011;71:460-73 pubmed publisher
    ..These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function. ..
  14. Berntsson R, Peng L, Dong M, Stenmark P. Structure of dual receptor binding to botulinum neurotoxin B. Nat Commun. 2013;4:2058 pubmed publisher
    ..The structure demonstrates that the protein receptor and the ganglioside receptor occupy nearby but separate binding sites, thus providing two independent anchoring points. ..
  15. Colvin R, Means T, Diefenbach T, Moita L, Friday R, Sever S, et al. Synaptotagmin-mediated vesicle fusion regulates cell migration. Nat Immunol. 2010;11:495-502 pubmed publisher
    ..proteins as mediators of cell migration: SYT7 and SYTL5 were positive regulators of chemotaxis, whereas SYT2 was a negative regulator of chemotaxis...
  16. Wu X, McNeil B, Xu J, Fan J, Xue L, Melicoff E, et al. Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal. Nat Neurosci. 2009;12:1003-1010 pubmed publisher
    ..Our findings provide a unifying mechanism for the initiation of various forms of endocytosis that are critical in maintaining exocytosis. ..
  17. Kochubey O, Babai N, Schneggenburger R. A Synaptotagmin Isoform Switch during the Development of an Identified CNS Synapse. Neuron. 2016;90:984-99 pubmed publisher
    ..At mature calyx synapses, fast Ca(2+)-driven transmitter release depended entirely on Syt2, but the release phenotype of Syt2 knockout (KO) mice was weaker at immature calyces, and absent at pre-calyceal ..
  18. Dong M, Tepp W, Liu H, Johnson E, Chapman E. Mechanism of botulinum neurotoxin B and G entry into hippocampal neurons. J Cell Biol. 2007;179:1511-22 pubmed
    ..These data suggest that gangliosides are the shared coreceptor for BoNT/A, B, and G, supporting a double-receptor model for these three BoNTs for which the protein receptors are known. ..
  19. Lang J. Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem. 1999;259:3-17 pubmed
    ..Insights into the progression of the exocytotic vesicle from docking to fusion and how these processes are precisely regulated by proteins and second messengers may provide the basis for new therapeutic principles. ..
  20. Lee B, Min X, Heise C, Xu B, Chen S, Shu H, et al. WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding. Mol Cell. 2004;15:741-51 pubmed
    ..Here, we report that WNK1 selectively binds to and phosphorylates synaptotagmin 2 (Syt2) within its calcium binding C2 domains...
  21. Tejero R, Lopez Manzaneda M, Arumugam S, Tabares L. Synaptotagmin-2, and -1, linked to neurotransmission impairment and vulnerability in Spinal Muscular Atrophy. Hum Mol Genet. 2016;25:4703-4716 pubmed publisher
    ..Additionally, the expression levels of synaptotagmin-2 (Syt2), and its interacting protein, synaptic vesicle protein 2 (SV2) B, were reduced in proportion to the degree of ..
  22. Luo F, Sudhof T. Synaptotagmin-7-Mediated Asynchronous Release Boosts High-Fidelity Synchronous Transmission at a Central Synapse. Neuron. 2017;94:826-839.e3 pubmed publisher
    ..Thus, asynchronous release surprisingly functions, at least at some synapses, to sustain high-fidelity neurotransmission driven by synchronous release during high-frequency stimulus trains. ..
  23. Sommeijer J, Levelt C. Synaptotagmin-2 is a reliable marker for parvalbumin positive inhibitory boutons in the mouse visual cortex. PLoS ONE. 2012;7:e35323 pubmed publisher
    ..We investigated whether synaptotagmin-2 (Syt2) fulfills these properties in the visual cortex...
  24. Fukuda M. Distinct developmental expression of synaptotagmin I and IX in the mouse brain. Neuroreport. 2006;17:179-82 pubmed
    ..These findings suggest that synaptotagmin IX regulates the transport of certain vesicles in the brain other than synaptic vesicles. ..
  25. Fukuda M, Aruga J, Niinobe M, Aimoto S, Mikoshiba K. Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. J Biol Chem. 1994;269:29206-11 pubmed
    b>IP4BP/Synaptotagmin II is an inositol-1,3,4,5-tetrakisphosphate (IP4) or inositol polyphosphate-binding protein, which is accumulated at nerve terminals...
  26. Tucker W, Edwardson J, Bai J, Kim H, Martin T, Chapman E. Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells. J Cell Biol. 2003;162:199-209 pubmed
    ..These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis. ..
  27. Fuerst P, Bruce F, Tian M, Wei W, Elstrott J, Feller M, et al. DSCAM and DSCAML1 function in self-avoidance in multiple cell types in the developing mouse retina. Neuron. 2009;64:484-97 pubmed publisher
    ..Therefore, DSCAM and DSCAML1 function similarly in self-avoidance, and are not essential for synaptic specificity in the mouse retina. ..
  28. Melicoff E, Sansores Garcia L, Gomez A, Moreira D, Datta P, Thakur P, et al. Synaptotagmin-2 controls regulated exocytosis but not other secretory responses of mast cells. J Biol Chem. 2009;284:19445-51 pubmed publisher
    ..Unlike neurons, the lack of Synaptotagmin-2 in mast cells was not associated with increased spontaneous exocytosis. ..
  29. Babai N, Kochubey O, Keller D, Schneggenburger R. An alien divalent ion reveals a major role for Ca²⁺ buffering in controlling slow transmitter release. J Neurosci. 2014;34:12622-35 pubmed publisher
    ..We show that Sr(2+) activates the fast, Synaptotagmin-2 (Syt2) sensor for vesicle fusion with sixfold lower affinity but unchanged high cooperativity...
  30. Choi H, Liu Y, Tennert C, Sugiura Y, Karakatsani A, Kroger S, et al. APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice. elife. 2013;2:e00220 pubmed publisher
    ..DOI: ..
  31. Bouhours B, Gjoni E, Kochubey O, Schneggenburger R. Synaptotagmin2 (Syt2) Drives Fast Release Redundantly with Syt1 at the Output Synapses of Parvalbumin-Expressing Inhibitory Neurons. J Neurosci. 2017;37:4604-4617 pubmed publisher
    ..Here, we investigated the roles of Syt1 and Syt2 at two types of fast-releasing inhibitory connections in the mammalian CNS: the medial nucleus of the trapezoid ..
  32. Lilley B, Pan Y, Sanes J. SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals. Neuron. 2013;79:39-53 pubmed publisher
    ..We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. ..
  33. Krishnaswamy A, Yamagata M, Duan X, Hong Y, Sanes J. Sidekick 2 directs formation of a retinal circuit that detects differential motion. Nature. 2015;524:466-470 pubmed publisher
    ..This non-canonical circuit introduces a delay into the pathway from photoreceptors in the centre of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion. ..
  34. Li P, Fu X, Smith N, Ziobro J, Curiel J, Tenga M, et al. Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy. Neuron. 2017;96:387-401.e6 pubmed publisher
    ..Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy. ..
  35. Sadakata T, Mizoguchi A, Sato Y, Katoh Semba R, Fukuda M, Mikoshiba K, et al. The secretory granule-associated protein CAPS2 regulates neurotrophin release and cell survival. J Neurosci. 2004;24:43-52 pubmed
    ..Thus, we suggest that CAPS2 mediates the depolarization-dependent release of NT-3 and BDNF from granule cells, leading to regulation in cell differentiation and survival during cerebellar development. ..
  36. Han C, Chen T, Yang M, Li N, Liu H, Cao X. Human SCAMP5, a novel secretory carrier membrane protein, facilitates calcium-triggered cytokine secretion by interaction with SNARE machinery. J Immunol. 2009;182:2986-96 pubmed publisher
    ..Our findings suggest that hSCAMP5, in cooperation with the SNARE machinery, is involved in calcium-regulated exocytosis of signal peptide-containing cytokines. ..
  37. Eom T, Zhang C, Wang H, Lay K, Fak J, Noebels J, et al. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. elife. 2013;2:e00178 pubmed publisher
    ..The data reveal a hidden means of dynamic RNA regulation linking electrical activity to splicing and protein output, and of mediating homeostatic excitation/inhibition balance in neurons.DOI: ..
  38. Tuvim M, Mospan A, Burns K, Chua M, Mohler P, Melicoff E, et al. Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum. J Biol Chem. 2009;284:9781-7 pubmed publisher
    b>Synaptotagmin 2 (Syt2) functions as a low affinity, fast exocytic Ca(2+) sensor in neurons, where it is activated by Ca(2+) influx through voltage-gated channels...
  39. Jones J, Popma S, Mizuta M, Seino S, Meisler M. Synaptotagmin genes on mouse chromosomes 1, 7, and 10 and human chromosome 19. Mamm Genome. 1995;6:212-3 pubmed
  40. Kochubey O, Schneggenburger R. Synaptotagmin increases the dynamic range of synapses by driving Ca²+-evoked release and by clamping a near-linear remaining Ca²+ sensor. Neuron. 2011;69:736-48 pubmed publisher
    ..We investigated the role of the Ca²+ sensor protein, Synaptotagmin2 (Syt2), in both spontaneous and Ca²+-evoked release under direct control of presynaptic [Ca²+](i), using an in vivo ..
  41. Beurg M, Michalski N, Safieddine S, Bouleau Y, Schneggenburger R, Chapman E, et al. Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells. J Neurosci. 2010;30:13281-90 pubmed publisher
    ..During this early exocytotic period, several synaptotagmins (Syts), including Syt1, Syt2 and Syt7, were detected in IHCs...
  42. Dorval V, Mandemakers W, Jolivette F, Coudert L, Mazroui R, De Strooper B, et al. Gene and MicroRNA transcriptome analysis of Parkinson's related LRRK2 mouse models. PLoS ONE. 2014;9:e85510 pubmed publisher
    ..e., <2 fold). By real-time quantitative RT-PCR, we confirmed the variations of selected genes (e.g., adra2, syt2, opalin) and miRNAs (e.g., miR-16, miR-25)...
  43. He L, Xue L, Xu J, McNeil B, Bai L, Melicoff E, et al. Compound vesicle fusion increases quantal size and potentiates synaptic transmission. Nature. 2009;459:93-7 pubmed publisher
    ..Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered. ..
  44. Fukuda M, Kojima T, Mikoshiba K. Phospholipid composition dependence of Ca2+-dependent phospholipid binding to the C2A domain of synaptotagmin IV. J Biol Chem. 1996;271:8430-4 pubmed
    ..However, it binds PS with a positive cooperativity and an affinity similar to those of the C2A domains of other isoforms. Our results suggest that synaptotagmin IV is also a potential Ca2+ sensor for neurotransmitter release. ..
  45. Chen C, Arai I, Satterfield R, Young S, Jonas P. Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse. Cell Rep. 2017;18:723-736 pubmed publisher
    ..Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals...
  46. Valente P, Castroflorio E, Rossi P, Fadda M, Sterlini B, Cervigni R, et al. PRRT2 Is a Key Component of the Ca(2+)-Dependent Neurotransmitter Release Machinery. Cell Rep. 2016;15:117-131 pubmed publisher
    ..The results indicate that PRRT2 is intimately connected with the Ca(2+)-sensing machinery and that it plays an important role in the final steps of neurotransmitter release. ..
  47. Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, et al. Autoregulation of neurogenesis by GDF11. Neuron. 2003;37:197-207 pubmed
  48. Fukuda M, Mikoshiba K. Genomic structures of synaptotagmin II protein: comparison of exon-intron organization of the synaptotagmin gene family. Biochem Biophys Res Commun. 2000;270:528-32 pubmed
    ..The only conserved feature among the synaptotagmin gene family seems to have a single exon that encodes the whole transmembrane domain. ..
  49. Tremblay M, Moss T. Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility. Cell Cycle. 2016;15:2360-6 pubmed publisher
    ..Most recently, we found that the genes for E-Syt2 and 3 could be inactivated without effect on mouse development, viability, fertility or morphology...
  50. Okamoto Y, Lipstein N, Hua Y, Lin K, Brose N, Sakaba T, et al. Distinct modes of endocytotic presynaptic membrane and protein uptake at the calyx of Held terminal of rats and mice. elife. 2016;5: pubmed publisher
    ..Membrane and Syt2 were retrieved with a similar time course when slow endocytosis was elicited...
  51. Dai J, Chen P, Tian H, Sun J. Spontaneous Vesicle Release Is Not Tightly Coupled to Voltage-Gated Calcium Channel-Mediated Ca2+ Influx and Is Triggered by a Ca2+ Sensor Other Than Synaptotagmin-2 at the Juvenile Mice Calyx of Held Synapses. J Neurosci. 2015;35:9632-7 pubmed publisher
  52. Liu Y, Sugiura Y, Wu F, Mi W, Taketo M, Cannon S, et al. ?-Catenin stabilization in skeletal muscles, but not in motor neurons, leads to aberrant motor innervation of the muscle during neuromuscular development in mice. Dev Biol. 2012;366:255-67 pubmed publisher