Drosophila AD3 mutation of synaptotagmin impairs calcium-dependent self- oligomerization activity

Mitsunori Fukuda, Hiroyuki Kabayama, Katsuhiko Mikoshiba

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Genetic analysis of a Drosophila synaptotagmin (Syt) I mutant (AD3) has revealed that Tyr-334 within the C2B domain is essential for efficient Ca2+-dependent neurotransmitter release. However, little is known as to why a missense mutation (Tyr-334-Asn) disrupts the function of the C2B domain at the molecular level. Here, we present evidence that a Tyr-312 to Asn substitution in mouse Syt II, which corresponds to the Drosophila AD3 mutation, completely impairs Ca2+-dependent self-oligomerization activity mediated by the C2B domain but allows partial interaction with wild-type proteins in a Ca2+-dependent manner. This observation is consistent with the fact that the AD3 allele is homozygous lethal but complements another mutant phenotype. We also showed that the Ca2+-dependent C2B self- oligomerization is inhibited by inositol 1,3,4,5-tetrakisphosphate, a potent inhibitor of neurotransmitter release. All of these findings strongly support the idea that self-oligomerization of Syt I or II is essential for neurotransmitter release in vivo. (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)269-272
Number of pages4
JournalFEBS Letters
Issue number3
Publication statusPublished - 2000 Oct 6
Externally publishedYes


  • C2 domain
  • Exocytosis
  • Self-oligomerization
  • Synaptic vesicle
  • Synaptotagmin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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