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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.

Subject(s)

Cyclin-Dependent Kinases/metabolism , Endocytosis/physiology , Synapses/metabolism , Synaptic Vesicles/metabolism , Amino Acid Motifs , Animals , Cyclin-Dependent Kinase 5 , Cyclin-Dependent Kinases/chemistry , Cyclin-Dependent Kinases/genetics , Dynamin I/genetics , Dynamin I/metabolism , Enzyme Inhibitors/metabolism , Monomeric Clathrin Assembly Proteins/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/cytology , Neurons/metabolism , Peptides/chemistry , Peptides/metabolism , Phosphorylation , Protein Kinase C/metabolism , Protein Kinase C-alpha , Purines/metabolism , Rats , Recombinant Fusion Proteins/metabolism , Roscovitine , Serine/metabolism , Sheep , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Synaptosomes/chemistry , Synaptosomes/metabolism , Synaptosomes/ultrastructure

ABSTRACT

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