synaptotagmin ii


Summary: A vesicular transport protein that was originally characterized as an inositol polyphosphate binding protein. Synaptotagmin II helps regulate EXOCYTOSIS of SYNAPTIC VESICLES and appears to serve as a calcium sensor to trigger NEUROTRANSMITTER release. It also acts as a nerve cell receptor for certain BOTULINUM TOXINS.

Top Publications

  1. Xu J, McNeil B, Wu W, Nees D, Bai L, Wu L. GTP-independent rapid and slow endocytosis at a central synapse. Nat Neurosci. 2008;11:45-53 pubmed
    ..The GTP- and dynamin-dependent pool has higher priority for release and retrieval, but limited capacity, saturation of which leads to release and thus retrieval of GTP- and dynamin-independent vesicles. ..
  2. Kida Y, Sakaguchi M, Fukuda M, Mikoshiba K, Mihara K. Membrane topogenesis of a type I signal-anchor protein, mouse synaptotagmin II, on the endoplasmic reticulum. J Cell Biol. 2000;150:719-30 pubmed
    b>Synaptotagmin II is a type I signal-anchor protein, in which the NH(2)-terminal domain of 60 residues (N-domain) is located within the lumenal space of the membrane and the following hydrophobic region (H-region) shows transmembrane ..
  3. 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. ..
  4. Frisk M, Lin G, Johnson E, Beebe D. Synaptotagmin II peptide-bead conjugate for botulinum toxin enrichment and detection in microchannels. Biosens Bioelectron. 2011;26:1929-35 pubmed publisher
    ..Micrometer-sized magnetic beads were conjugated to a 22mer synthetic peptide derived from the synaptotagmin II (Syt II) neuronal protein that is specific for BoNT/B binding...
  5. Zhou Y, Foss S, Lindo P, Sarkar H, Singh B. Hemagglutinin-33 of type A botulinum neurotoxin complex binds with synaptotagmin II. FEBS J. 2005;272:2717-26 pubmed
    ..Using immunoaffinity column chromatography and pull-down assays, we have now discovered that Hn-33 binds to synaptotagmin II, the putative receptor of botulinum neurotoxin...
  6. 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
    ..Here we report the crystal structure of full-length BoNT/B in complex with the synaptotagmin II (Syt-II) recognition domain at 2.6 A resolution...
  7. Jin R, Rummel A, Binz T, Brunger A. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature. 2006;444:1092-5 pubmed
    ..the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution...
  8. 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. ..
  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. 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
    IP4BP/Synaptotagmin II is an inositol-1,3,4,5-tetrakisphosphate (IP4) or inositol polyphosphate-binding protein, which is accumulated at nerve terminals...
  2. 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. ..
  3. Strotmeier J, Willjes G, Binz T, Rummel A. Human synaptotagmin-II is not a high affinity receptor for botulinum neurotoxin B and G: increased therapeutic dosage and immunogenicity. FEBS Lett. 2012;586:310-3 pubmed publisher
  4. Lindmark I, Karlsson A, Serrander L, Francois P, Lew D, Rasmusson B, et al. Synaptotagmin II could confer Ca(2+) sensitivity to phagocytosis in human neutrophils. Biochim Biophys Acta. 2002;1590:159-66 pubmed
    ..In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes...
  5. Peng Z, Grimberg E, Sagi Eisenberg R. Suppression of Synaptotagmin II restrains phorbolester-induced downregulation of protein kinase Calpha by diverting the kinase from a degradative pathway to the recycling endocytic compartment. J Cell Sci. 2002;115:3083-92 pubmed
    ..In this study, we show that synaptotagmin II (Syt II), a member of the Syt family of proteins, is required for TPA-induced degradation of PKCalpha...
  6. Xu J, Mashimo T, Sudhof T. Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron. 2007;54:567-81 pubmed
  7. 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
  8. 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 propose a dual-Ca2+-sensor model of release that quantitatively describes the contributions of synchronous and asynchronous release under conditions of different presynaptic Ca2+ dynamics. ..
  9. Young S, Neher E. Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor. Neuron. 2009;63:482-96 pubmed publisher
  10. 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
    ..We conclude that exocytosis from mouse chromaffin cells can be modified by the differential expression of Syt isoforms and by Syt abundance but not by phosphorylation of Syt1. ..
  11. Geppert M, Archer B, Sudhof T. Synaptotagmin II. A novel differentially distributed form of synaptotagmin. J Biol Chem. 1991;266:13548-52 pubmed
    ..C. (1990) Nature 345, 260-263). Here, we report the structure of a novel form of synaptotagmin named synaptotagmin II that is highly homologous to the originally described synaptotagmin, now referred to as synaptotagmin I...
  12. 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. ..
  13. 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
  14. Baram D, Adachi R, Medalia O, Tuvim M, Dickey B, Mekori Y, et al. Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells. J Exp Med. 1999;189:1649-58 pubmed
    ..These findings provide evidence for a novel function of Syt II in negatively regulating Ca2+-triggered exocytosis of lysosomes, and suggest that Syt II-regulated secretion from lysosomes may play an important role in mast cell biology. ..
  15. 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. ..
  16. Murakumo Y, Takahashi M, Sharma N, Arakawa A, Saito M, Amo H, et al. Mapping of two genetic loci, Ten-1 and Ten-2, associated with thymus enlargement in BUF/Mna rats. Mamm Genome. 1996;7:505-8 pubmed
    ..Ten-1 was located between myosin light chain, muscle 2 (MYL2) and D1Mgh11 loci on Chr 1, and Ten-2 was located between synaptotagmin II (SYT2) and D13N2 loci on Chr 13.
  17. Cooper A, Gillespie D. Synaptotagmins I and II in the developing rat auditory brainstem: Synaptotagmin I is transiently expressed in glutamate-releasing immature inhibitory terminals. J Comp Neurol. 2011;519:2417-33 pubmed publisher
  18. 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. ..
  19. Johnsson A, Karlsson R. Synaptotagmin 1 causes phosphatidyl inositol lipid-dependent actin remodeling in cultured non-neuronal and neuronal cells. Exp Cell Res. 2012;318:114-26 pubmed publisher
  20. Fukuda M, Mikoshiba K. Expression of synaptotagmin I or II promotes neurite outgrowth in PC12 cells. Neurosci Lett. 2000;295:33-6 pubmed
    ..These results indicate the Ca(2+)/phospholipid binding site of Syt I or II to be essential for neurite outgrowth. ..
  21. Chen G, Muramatsu H, Kondo M, Kurosawa N, Miyake Y, Takeda N, et al. Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice. Mol Cell Biol. 2005;25:7828-38 pubmed
    ..However, cataracts did not develop earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and synaptotagmin VII, were found in the kidney of the deficient mice and correlated with renal abnormalities. ..
  22. Willjes G, Mahrhold S, Strotmeier J, Eichner T, Rummel A, Binz T. Botulinum neurotoxin G binds synaptotagmin-II in a mode similar to that of serotype B: tyrosine 1186 and lysine 1191 cause its lower affinity. Biochemistry. 2013;52:3930-8 pubmed publisher
    ..These data suggest a reduced length and/or a bend in the C-terminal part of the synaptotagmin helix that forms upon contact with BoNT/G as compared with BoNT/B and are in agreement with the data of the mutational analyses. ..
  23. Berntsson R, Peng L, Dong M, Stenmark P. Structure of dual receptor binding to botulinum neurotoxin B. Nat Commun. 2013;4:2058 pubmed publisher
    ..3-Å structure of a ternary complex of botulinum neurotoxin type B bound to both its protein receptor synaptotagmin II and its ganglioside receptor GD1a...
  24. Elfving B, Bonefeld B, Rosenberg R, Wegener G. Differential expression of synaptic vesicle proteins after repeated electroconvulsive seizures in rat frontal cortex and hippocampus. Synapse. 2008;62:662-70 pubmed publisher
    ..We suggest that these genes are highly important in the long-term therapeutic effect of ECS, and thus it can be hypothesized that the SVPs are involved in the pathophysiology of depression. ..
  25. Ebrahimi F, Rasaee M, Mousavi S, Babaeipour V. Production and characterization of a recombinant chimeric antigen consisting botulinum neurotoxin serotypes A, B and E binding subdomains. J Toxicol Sci. 2010;35:9-19 pubmed
    ..We conclude that a significant correlation exists between the antigenic characteristics and protection capability of the chimeric protein prepared in this study. ..
  26. Nagai Y, Tadokoro S, Sakiyama H, Hirashima N. Effects of synaptotagmin 2 on membrane fusion between liposomes that contain SNAREs involved in exocytosis in mast cells. Biochim Biophys Acta. 2011;1808:2435-9 pubmed publisher
  27. Dolimbek B, Steward L, Aoki K, Atassi M. The binding sites on botulinum neurotoxin B for synaptotagmin and for blocking antibodies. Biochem Biophys Res Commun. 2008;376:631-2 pubmed publisher
  28. Jean S, Mikryukov A, Tremblay M, Baril J, Guillou F, Bellenfant S, et al. Extended-synaptotagmin-2 mediates FGF receptor endocytosis and ERK activation in vivo. Dev Cell. 2010;19:426-39 pubmed publisher
    ..The data identify E-Syt2 as an endocytic adaptor for the clathrin-mediated pathway whose function is conserved in human and suggest a broader role for the E-Syt subfamily in growth factor signaling. ..
  29. Wang H, Han S, Siao W, Song C, Xiang Y, Wu X, et al. Arabidopsis Synaptotagmin 2 Participates in Pollen Germination and Tube Growth and Is Delivered to Plasma Membrane via Conventional Secretion. Mol Plant. 2015;8:1737-50 pubmed publisher
    ..Take together, our results indicated that SYT2 was required for pollen germination and pollen tube growth, and was involved in conventional exocytosis. ..
  30. Heidelberger R. Neuroscience: sensors and synchronicity. Nature. 2007;450:623-5 pubmed
  31. Kida Y, Sakaguchi M, Fukuda M, Mikoshiba K, Mihara K. Amino acid residues before the hydrophobic region which are critical for membrane translocation of the N-terminal domain of synaptotagmin II. FEBS Lett. 2001;507:341-5 pubmed
    We examined the fine structure of the type I signal-anchor sequence of synaptotagmin II, which has a 60-residue N-terminal domain followed by a hydrophobic region (H-region), focusing on the hinge region between the N-terminal and the H-..
  32. Charvin N, L evêque C, Walker D, Berton F, Raymond C, Kataoka M, et al. Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel. EMBO J. 1997;16:4591-6 pubmed
    ..Direct synaptotagmin binding to the pore-forming subunit of the P/Q-type channel may optimally locate the calcium-binding sites that initiate exocytosis within a zone of voltage-gated calcium entry. ..
  33. Stevens C, Sullivan J. The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission. Neuron. 2003;39:299-308 pubmed
    ..We conclude that neutralization of the negative charge at D232 by coordination of a calcium ion is necessary--but not sufficient--for fast neurotransmission at mammalian CNS synapses. ..
  34. Zhang J, Lu W, Li Y, Wu J, Zhang C. Anti-sense RNA inhibits the expression of synaptotagmin II in RBL-2H3 and enhances the exocytosis of lysosomes in RBL-2H3. J Huazhong Univ Sci Technolog Med Sci. 2005;25:117-20 pubmed
    The expression of synaptotagmin II (Syt2) in RBL-2H3 (RBL) and its role during exocytosis of RBL was investigated. The expression of Syt2 in RBL was detected by western blot and Syt2 gene was amplified by PCR...
  35. Shao M, Reddaway R, Hirsch J, Peusner K. Presynaptic GABA(B) receptors decrease neurotransmitter release in vestibular nuclei neurons during vestibular compensation. Neuroscience. 2012;223:333-54 pubmed publisher
  36. Wakana Y, van Galen J, Meissner F, Scarpa M, Polishchuk R, Mann M, et al. A new class of carriers that transport selective cargo from the trans Golgi network to the cell surface. EMBO J. 2012;31:3976-90 pubmed publisher
    ..kinase D (PKD) is required for the biogenesis of these carriers that contain myosin II, Rab6a, Rab8a, and synaptotagmin II, as well as a number of secretory and plasma membrane-specific cargoes...
  37. 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. ..
  38. 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
    ..We suggest that otoferlin underlies highly efficient Ca(2+)-dependent membrane-membrane fusion, a process likely essential to increase the probability and synchrony of vesicle fusion events at the mature IHC ribbon synapse. ..
  39. Shi J, Li T, Hou X, Cai K, Bao S, Liu H, et al. Recombinant luminal domain of human synaptotagmin II in combination with gangliosides inhibits the toxicity of botulinum neurotoxins in mice. Microbes Infect. 2010;12:319-23 pubmed publisher
    b>Synaptotagmin II (syt II) is the specific protein receptor of botulinum neurotoxin B (BoNT/B), and the luminal domain of syt II contains toxin-binding sites that have a high affinity for BoNT/B...
  40. 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
    ..Hence, Syt2 can serve as an exocytic sensor for diverse Ca(2+) signaling systems, and its levels are limiting for stimulated secretory function in airway goblet cells. ..
  41. Pang Z, Xu W, Cao P, Sudhof T. Calmodulin suppresses synaptotagmin-2 transcription in cortical neurons. J Biol Chem. 2010;285:33930-9 pubmed publisher
    ..Our data describe a previously unknown, Ca(2+)/CaM-dependent regulatory pathway that controls the expression of synaptic proteins in the rostral-caudal neuraxis. ..
  42. Garcia R, Godwin H. High metal concentrations are required for self-association of synaptotagmin II. Biophys J. 2004;86:2455-66 pubmed
    ..In addition, the high propensity of lead to oligomerize syt II offers a possible molecular explanation for how lead interferes with calcium-evoked neurotransmitter release. ..
  43. Liu Y, Brent G. Thyroid hormone-dependent gene expression in differentiated embryonic stem cells and embryonal carcinoma cells: identification of novel thyroid hormone target genes by deoxyribonucleic acid microarray analysis. Endocrinology. 2005;146:776-83 pubmed
    ..RNA-binding protein (SPNR), kallikrein-binding protein (KBP), prostate-specific membrane antigen (PSMA), and synaptotagmin II, for more detailed study...
  44. Angaut Petit D, Molgo J, Faille L, Juzans P, Takahashi M. Incorporation of synaptotagmin II to the axolemma of botulinum type-A poisoned mouse motor endings during enhanced quantal acetylcholine release. Brain Res. 1998;797:357-60 pubmed
    ..or La3+ in conditions that prevent endocytosis, and an antibody directed against the lumenal domain of synaptotagmin II (Syt II) was used in the presence or absence of Triton X-100...
  45. Atiya Nasagi Y, Cohen H, Medalia O, Fukudan M, Sagi Eisenberg R. O-glycosylation is essential for intracellular targeting of synaptotagmins I and II in non-neuronal specialized secretory cells. J Cell Sci. 2005;118:1363-72 pubmed
    ..Our results indicate that the luminal domains of Syt I and Syt II govern their internalization capacity from the plasma membrane and identify O-glycosylation as playing a crucial role in Syt trafficking in non-neuronal secretory cells. ..
  46. Fukuda M, Kojima T, Aruga J, Niinobe M, Mikoshiba K. Functional diversity of C2 domains of synaptotagmin family. Mutational analysis of inositol high polyphosphate binding domain. J Biol Chem. 1995;270:26523-7 pubmed
    ..The IP4 binding domain of synaptotagmin II is characterized by a cluster of highly conserved, positively charged amino acids (321 GKRLKKKKTTVKKK 324)...
  47. Westerink R, Klompmakers A, Westenberg H, Vijverberg H. Signaling pathways involved in Ca2+- and Pb2+-induced vesicular catecholamine release from rat PC12 cells. Brain Res. 2002;957:25-36 pubmed
    ..It is concluded that Ca(2+)-evoked exocytosis is modulated mainly by PKC and calcineurin, whereas Pb(2+)-evoked exocytosis is mainly modulated by CaM kinase II. ..
  48. Sakaguchi M. [Topogenesis of membrane proteins: ER system and escape from ER targeting]. Seikagaku. 2003;75:520-8 pubmed
  49. Wang H, Li T, Shi J, Cai K, Hou X, Wang Q, et al. A new neutralizing antibody against botulinum neurotoxin B recognizes the protein receptor binding sites for synaptotagmins II. Microbes Infect. 2010;12:1012-8 pubmed publisher
    ..Information gained from this study will facilitate the development of potent inhibitors that prevent the binding of BoNts with its receptors. ..
  50. Xi D, Chin H, Gainer H. Analysis of synaptotagmin I-IV messenger RNA expression and developmental regulation in the rat hypothalamus and pituitary. Neuroscience. 1999;88:425-35 pubmed
    ..4- or 38-fold higher in hypothalamus than in neurointermediate and anterior pituitary lobe, respectively. Synaptotagmin II, which is very abundant in cerebellum, is relatively low in hypothalamus (5% of cerebellum) and virtually ..
  51. Baram D, Peng Z, Medalia O, Mekori Y, Sagi Eisenberg R. Synaptotagmin II negatively regulates MHC class II presentation by mast cells. Mol Immunol. 2002;38:1347-52 pubmed
    ..b>Synaptotagmin II is located at the late/endosomal/lysosomal compartment, where it negatively regulates lysosomal exocytosis...
  52. Berntsson R, Peng L, Svensson L, Dong M, Stenmark P. Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II. Structure. 2013;21:1602-11 pubmed publisher
    ..The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs. ..
  53. Wässle H, Puller C, Muller F, Haverkamp S. Cone contacts, mosaics, and territories of bipolar cells in the mouse retina. J Neurosci. 2009;29:106-17 pubmed publisher
    ..The quantitative analysis suggests that our proposed catalog of 11 cone bipolar cells and one rod bipolar cell is complete, and all major bipolar cell types of the mouse retina appear to have been discovered. ..