Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C

Cai Li, Kohji Takei, Martin Geppert, Laurie Daniell, Katinka Stenius, Edwin R. Chapman, Reinhard Jahn, Pietro De Camilli, Thomas C. Südhof

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

rab3A, a low molecular weight GTP-binding protein of synaptic vesicles with a putative function in synaptic vesicle docking, interacts in a GTP-dependent manner with rabphilin-3A, a peripheral membrane protein that binds Call and phospholipids. We now show that rabphilin-3A is an evolutionarily conserved synaptic vesicle protein that is attached to synaptic vesicle membranes via its N terminus and exhibits a heterogeneous distribution among synapses. In rab3A-deficient mice, rabphilin-3A is decreased in synapses belonging to neurons that primarily express rab3A and accumulates in the perikarya of these neurons. In contrast, neurons expressing significant levels of rab3C still contain normal levels of rabphilin-3A in a synaptic pattern, and rabphilin-3A binds rab3C in vitro. These results suggest that analogous to the membrane recruitment of raf by ras, rab3A and rab3C may function in recruiting .rabphilin-3A to the synaptic vesicle membrane in a GTP-dependent manner.

Original languageEnglish
Pages (from-to)885-898
Number of pages14
JournalNeuron
Volume13
Issue number4
DOIs
Publication statusPublished - Oct 1994
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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