Doc2b Is a High-Affinity Ca2+ Sensor for Spontaneous Neurotransmitter Release

AJ Groffen, RD Arazola, LN Cornelisse, N Lozovaya, APH de Jong, NA Goriounova, RLP (Ron) Habets, Y Takai, Gerard Borst, N Brose, HT McMahon, M (Matthijs) Verhage

Research output: Contribution to journalArticleAcademicpeer-review

234 Citations (Scopus)

Abstract

Synaptic vesicle fusion in brain synapses occurs in phases that are either tightly coupled to action potentials ( synchronous), immediately following action potentials (asynchronous), or as stochastic events in the absence of action potentials (spontaneous). Synaptotagmin-1, -2, and -9 are vesicle-associated Ca2+ sensors for synchronous release. Here we found that double C2 domain (Doc2) proteins act as Ca2+ sensors to trigger spontaneous release. Although Doc2 proteins are cytosolic, they function analogously to synaptotagmin-1 but with a higher Ca2+ sensitivity. Doc2 proteins bound to N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complexes in competition with synaptotagmin-1. Thus, different classes of multiple C2 domain-containing molecules trigger synchronous versus spontaneous fusion, which suggests a general mechanism for synaptic vesicle fusion triggered by the combined actions of SNAREs and multiple C2 domain-containing proteins.
Original languageUndefined/Unknown
Pages (from-to)1614-1618
Number of pages5
JournalScience
Volume327
Issue number5973
DOIs
Publication statusPublished - 2010

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