Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment.

Journal Article (Journal Article)

Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is ubiquitously expressed, yet its function in neurons remains obscure. Here, we resolved Ca(2+)-dependent and Ca(2+)-independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca(2+)-dependent pathway. Mutations that disrupt Ca(2+)-binding to syt 7 abolish this function, suggesting that syt 7 functions as a Ca(2+)-sensor for replenishment. The Ca(2+)-binding protein calmodulin (CaM) has also been implicated in SV replenishment, and we found that loss of syt 7 was phenocopied by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly specific and Ca(2+)-dependent manner; this interaction requires intact Ca(2+)-binding sites within syt 7. Together, these data indicate that a complex of two conserved Ca(2+)-binding proteins, syt 7 and CaM, serve as a key regulator of SV replenishment in presynaptic nerve terminals. DOI: http://dx.doi.org/10.7554/eLife.01524.001.

Full Text

Duke Authors

Cited Authors

  • Liu, H; Bai, H; Hui, E; Yang, L; Evans, CS; Wang, Z; Kwon, SE; Chapman, ER

Published Date

  • February 25, 2014

Published In

Volume / Issue

  • 3 /

Start / End Page

  • e01524 -

PubMed ID

  • 24569478

Pubmed Central ID

  • PMC3930910

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.01524

Language

  • eng

Conference Location

  • England