Gene Symbol: Syt4
Description: synaptotagmin IV
Alias: SytIV, synaptotagmin-4
Species: mouse
Products:     Syt4

Top Publications

  1. Ferguson G, Wang H, Herschman H, Storm D. Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice. Hippocampus. 2004;14:964-74 pubmed
    ..These results suggest Syt IV is a presynaptic negative regulator of short-term plasticity in area CA1 of the hippocampus and is required for some, but not all, forms of hippocampus-dependent memory. ..
  2. Vician L, Lim I, Ferguson G, Tocco G, Baudry M, Herschman H. Synaptotagmin IV is an immediate early gene induced by depolarization in PC12 cells and in brain. Proc Natl Acad Sci U S A. 1995;92:2164-8 pubmed
    ..Sequencing identified the protein product of this gene as rat synaptotagmin IV (SytIV)...
  3. Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon P. Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci U S A. 2004;101:9441-6 pubmed
  4. Ibata K, Hashikawa T, Tsuboi T, Terakawa S, Liang F, Mizutani A, et al. Non-polarized distribution of synaptotagmin IV in neurons: evidence that synaptotagmin IV is not a synaptic vesicle protein. Neurosci Res. 2002;43:401-6 pubmed
    ..These results suggest that Syt IV regulates non-polarized membrane trafficking in neurons, which may be involved in synaptic plasticity or neuronal development. ..
  5. Ferguson G, Anagnostaras S, Silva A, Herschman H. Deficits in memory and motor performance in synaptotagmin IV mutant mice. Proc Natl Acad Sci U S A. 2000;97:5598-603 pubmed
    ..These studies demonstrate that Syt IV is critical for brain function and suggest that the Syt IV mutation affects hippocampal-dependent learning and memory, as well as motor coordination. ..
  6. Aoki H, Hara A, Era T, Kunisada T, Yamada Y. Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis. Development. 2012;139:667-77 pubmed publisher
    ..Our findings highlight the significance of extrinsic signals for the proper intrinsic regulation of neuronal gene expression levels in the specification of cell fate during embryonic neurogenesis in vivo. ..
  7. Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011;69:523-35 pubmed publisher
    ..In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases. ..
  8. Ferguson G, Chen X, Korenberg J, Herschman H. The human synaptotagmin IV gene defines an evolutionary break point between syntenic mouse and human chromosome regions but retains ligand inducibility and tissue specificity. J Biol Chem. 2000;275:36920-6 pubmed
    ..Within brain, human SYT IV mRNA is most highly expressed in hippocampus, with lower levels present in amygdala and thalamus. These results suggest a role for SYT IV in human brain function and in human neurological disease. ..
  9. Perin M, Fried V, Mignery G, Jahn R, Sudhof T. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature. 1990;345:260-3 pubmed
    ..The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis. ..

More Information


  1. Hunt C, Parsian A, Kozak C. Genetic mapping of mouse heat shock protein genes Hsc4a to chromosome 11 and Hsc74 to chromosome 18 and two Hsc74 pseudogenes to chromosomes X and 8. Genomics. 1999;56:358-60 pubmed
  2. Kwon O, Adamson M, Chin H, Kozak C. Genetic mapping of five mouse genes encoding synaptotagmins. Mamm Genome. 1995;6:880-1 pubmed
  3. 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
  4. Aoki H, Hara A, Oomori Y, Shimizu Y, Yamada Y, Kunisada T. Neonatal lethality of neural crest cell-specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus. Genes Cells. 2014;19:723-42 pubmed publisher
    ..The observed gastrointestinal distension phenotype provides a model for understanding the genetic and molecular basis of NCC defects in humans. ..
  5. Hilbush B, Morgan J. A third synaptotagmin gene, Syt3, in the mouse. Proc Natl Acad Sci U S A. 1994;91:8195-9 pubmed
    ..This result suggests that individual neurons may have specific combinations of synaptotagmins that could provide for diversity in vesicular release. ..
  6. Ferguson G, Herschman H, Storm D. Reduced anxiety and depression-like behavior in synaptotagmin IV (-/-) mice. Neuropharmacology. 2004;47:604-11 pubmed
    ..These results indicate that Syt IV plays a role in rodent mood-related behavior and suggests Syt IV regulates synaptic function in the neuronal networks that modulate these behaviors. ..
  7. Ballas N, Grunseich C, Lu D, Speh J, Mandel G. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell. 2005;121:645-657 pubmed publisher
    ..Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli. ..
  8. Castro D, Martynoga B, Parras C, Ramesh V, Pacary E, Johnston C, et al. A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. Genes Dev. 2011;25:930-45 pubmed publisher
  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. Dean C, Liu H, Staudt T, Stahlberg M, Vingill S, Bückers J, et al. Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity. J Neurosci. 2012;32:5398-413 pubmed publisher
  11. Kumar A, Thakur M. Analysis of Presenilin 1 and 2 interacting proteins in mouse cerebral cortex during development. Int J Dev Neurosci. 2014;38:138-46 pubmed publisher
  12. Mendez J, Bourque M, Fasano C, Kortleven C, Trudeau L. Somatodendritic dopamine release requires synaptotagmin 4 and 7 and the participation of voltage-gated calcium channels. J Biol Chem. 2011;286:23928-37 pubmed publisher
    ..Down-regulation of the dendritically expressed Syt4 and Syt7 severely reduced STD DA release, whereas terminal release required Syt1...
  13. Johnson S, Franz C, Kuhn S, Furness D, Rüttiger L, Münkner S, et al. Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses. Nat Neurosci. 2010;13:45-52 pubmed publisher
    ..We propose that the differential expression of synaptotagmins determines the characteristic Ca(2+) sensitivity of vesicle fusion at hair cell synapses. ..
  14. Dean C, Liu H, Dunning F, Chang P, Jackson M, Chapman E. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release. Nat Neurosci. 2009;12:767-76 pubmed publisher
    ..Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP. ..
  15. Zhang Z, Bhalla A, Dean C, Chapman E, Jackson M. Synaptotagmin IV: a multifunctional regulator of peptidergic nerve terminals. Nat Neurosci. 2009;12:163-71 pubmed publisher
    ..Given the neuroendocrine functions of the posterior pituitary, changes in Syt IV levels could be involved in endocrine transitions involving alterations in the release of the neuropeptides oxytocin and vasopressin. ..
  16. Hu Z, Chen M, Ping Z, Dong Y, Zhang R, Xu T, et al. Synaptotagmin IV regulates dense core vesicle (DCV) release in LbetaT2 cells. Biochem Biophys Res Commun. 2008;371:781-6 pubmed publisher
    ..Downregulation of Syt IV clearly reduced Ca(2+)-triggered exocytosis of dense core vesicles (DCVs) in LbetaT2 cells. Syt I silencing, however, had no effect on vesicular release. ..
  17. 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. ..
  18. Willison K. The mouse Brachyury gene and mesoderm formation. Trends Genet. 1990;6:104-5 pubmed
  19. Arthur C, Dean C, Pagratis M, Chapman E, Stowell M. Loss of synaptotagmin IV results in a reduction in synaptic vesicles and a distortion of the Golgi structure in cultured hippocampal neurons. Neuroscience. 2010;167:135-42 pubmed publisher
    ..The proportion of docked vesicles in syt IV -/- boutons was further reduced, 5-fold, following depolarization. ..
  20. Fukuda M, Kanno E, Mikoshiba K. Conserved N-terminal cysteine motif is essential for homo- and heterodimer formation of synaptotagmins III, V, VI, and X. J Biol Chem. 1999;274:31421-7 pubmed
  21. 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. ..