Cdk5 is essential for synaptic vesicle endocytosis |
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Authors: | 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 |
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Institution: | Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia. |
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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 cyclin-dependent 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. |
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