Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth

Katsuhiko Mikoshiba, Mitsunori Fukuda, Keiji Ibata, Hiroyuki Kabayama, Akihiro Mizutani

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Synaptotagmin I (or II), a possible Ca2+-sensor of synaptic vesicles, has two functionally distinct C2 domains: the C2A domain binds Ca2+and the C2B domain binds inositol high polyphosphates (IP4, IP5, and IP6). Ca2+-regulated exocytosis of secretory vesicles is proposed to be activated by Ca2+ binding to the C2A domain and inhibited by inositol polyphosphate binding to the C2B domain. Synaptotagmins now constitute a large family and are thought to be involved in both regulated and constitutive vesicular trafficking. They are classified from their distribution as neuronal (synaptotagmin I-V, X, and XI) and the ubiquitous type (synaptotagmin VI-IX). Among them, synaptotagmins III, V, VI and X are deficient in IP4 binding activity due to the amino acid substitutions in the C-terminal region of the C2B domain, suggesting that these isoforms can work for vesicular trafficking even in the presence of inositol high polyphosphates. Synaptotagmin I is also known to be present in neuronal growth cone vesicles. Antibody against the C2A domain (anti-C2A) that inhibits Ca2+-regulated exocytosis also blocked neurite outgrowth of the chick dorsal root ganglion (DRG) neuron, suggesting that Ca2+-dependent synaptotagmin activation is also crucial for neurite outgrowth. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalChemistry and Physics of Lipids
Volume98
Issue number1-2
DOIs
Publication statusPublished - 1999 Apr
Externally publishedYes

Fingerprint

Synaptotagmins
Polyphosphates
Synaptotagmin I
Inositol
Neurotransmitter Agents
Carrier Proteins
Synaptotagmin II
Exocytosis
Neurons
Cones
Protein Isoforms
Substitution reactions
Chemical activation
Growth Cones
Synaptic Vesicles
Amino Acids
Secretory Vesicles
Spinal Ganglia
Amino Acid Substitution
Neuronal Outgrowth

Keywords

  • Neurite outgrowth
  • Neurotransmitter release
  • Synaptotagmin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth. / Mikoshiba, Katsuhiko; Fukuda, Mitsunori; Ibata, Keiji; Kabayama, Hiroyuki; Mizutani, Akihiro.

In: Chemistry and Physics of Lipids, Vol. 98, No. 1-2, 04.1999, p. 59-67.

Research output: Contribution to journalArticle

Mikoshiba, Katsuhiko ; Fukuda, Mitsunori ; Ibata, Keiji ; Kabayama, Hiroyuki ; Mizutani, Akihiro. / Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth. In: Chemistry and Physics of Lipids. 1999 ; Vol. 98, No. 1-2. pp. 59-67.
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