title: Synapsin I-associated phosphatidylinositol 3-kinase mediates synaptic vesicle delivery to the readily releasable pool.
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.
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville 2145, NSW, Australia. m.cousin@ed.ac.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cousin
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Malladi
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Tan
authors.forename: Clarke R
authors.initials: CR
authors.lastname: Raymond
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Smillie
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism; D009473:Neuronal Plasticity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D018698:Glutamic Acid; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016704:Synapsins; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one