Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/Synaptotagmin II

Mitsunori Fukuda, Jun Aruga, Michio Niinobe, Saburo Aimoto, Katsuhiko Mikoshiba

Research output: Contribution to journalArticlepeer-review

233 Citations (Scopus)

Abstract

IP4BP/Synaptotagmin II is an inositol-1,3,4,5-tetrakisphosphate (IP4) or inositol polyphosphate-binding protein, which is accumulated at nerve terminals. Here we report a novel function of the C2B domain, which was originally thought to be responsible for Ca2+-dependent binding to phospholipid membranes. A study of deletion mutants showed that about 30 amino acids of the central region of the C2B domain of mouse IP4BP/synaptotagmin II (315 IHLMQNGKRLKKKKTTVKKKTLNPYFNESFSF 346) are essential for inositol polyphosphate binding. This binding domain includes a sequence corresponding to the squid Pep20 peptide, which is also known to be essential for neurotransmitter release (Bommert, K., Charlton, M. P., DeBello, W. M., Chin, G. J., Betz, H., and Augustine, G. J. (1993) Nature 363, 163-165), suggesting that inositol polyphosphate has some effect on neurotransmitter release. Rabphilin 3A, another neuronal protein containing C2 domains, cannot bind IP4, indicating that the IP4 binding property is specific to the C2B domain of synaptotagmin. Phospholipid and IP4 binding experiments clearly indicated that the C2A and C2B domains have different functions. The C2A domain binds phospholipid in a Ca2+-dependent manner, but the C2B domain binds inositol polyphosphate and phospholipid irrespective of the presence of Ca2+. Our data suggest that the C2B domain of synaptotagmin is the inositol polyphosphate sensor at the synaptic vesicle and may be involved in synaptic function.

Original languageEnglish
Pages (from-to)29206-29211
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number46
Publication statusPublished - 1994 Nov 18
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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