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

FEBS Letters

Fukuda, Mitsunori¹  Mikoshiba, Katsuhiko¹  Kabayama, Hiroyuki¹ 

[1] Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

关键词: Synaptotagmin;    C2 domain;    Self-oligomerization;    Exocytosis;    Synaptic vesicle;    HRP;    horseradish peroxidase;    IP4;    D/L-myo-inositol 1;    3;    4;    5-tetrakisphosphate;    Syt(s);    synaptotagmin(s);   

DOI  :  10.1016/S0014-5793(00)02064-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown