Synapsin I-associated phosphatidylinositol 3-kinase mediates synaptic vesicle delivery to the readily releasable pool

Michael A. Cousin*, Chandra S. Malladi, Timothy C. Tan, Clarke R. Raymond, Karen J. Smillie, Phillip J. Robinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Maintaining synaptic transmission requires replenishment of docked synaptic vesicles within the readily releasable pool (RRP) from synaptic vesicle clusters in the synapsin-bound reserve pool. We show that synapsin forms a complex with phosphatidylinositol 3-kinase (PI 3-kinase) in intact nerve terminals and that synapsin-associated kinase activity increases on depolarization. Disruption of either PI 3-kinase activity or its interaction with synapsin inhibited replenishment of the RRP, but did not affect exocytosis from the RRP. Thus we conclude that a synapsin-associated PI 3-kinase activity plays a role in synaptic vesicle delivery to the RRP. This also suggests that PI 3-kinase contributes to the maintenance of synaptic transmission during periods of high activity, indicating a possible role in synaptic plasticity.

Original languageEnglish
Pages (from-to)29065-29071
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
Publication statusPublished - 1 Aug 2003

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