Cdk5 is essential for synaptic vesicle endocytosis
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Date
08/2003Author
Tan, Timothy C
Valova, Valentina A
Malladi, Chandra S
Graham, Mark E
Berven, Leise A
Jupp, Orla J
Hansra, Gurdip
McClure, Sonya J
Sarcevic, Boris
Boadle, Ross A
Larsen, Martin R
Cousin, Michael A
Robinson, Phillip J
Metadata
Abstract
Synaptic vesicle endocytosis (SVE) is triggered by calcineurin-mediated dephosphorylation of the dephosphin proteins. SVE is
maintained by the subsequent rephosphorylation of the dephosphins by unidentified protein kinases. Here, we show that cyclindependent
kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous
phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I,
but not of amphiphysin or AP180, in nerve terminals and inhibit SVE. Thus Cdk5 has an essential role in SVE and is the first
dephosphin kinase identified in nerve terminals.