title: Cdk5 is essential for synaptic vesicle endocytosis.
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.
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Tan
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Valova
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Malladi
authors.forename: Mark E
authors.initials: ME
authors.lastname: Graham
authors.forename: Leise A
authors.initials: LA
authors.lastname: Berven
authors.forename: Orla J
authors.initials: OJ
authors.lastname: Jupp
authors.forename: Gurdip
authors.initials: G
authors.lastname: Hansra
authors.forename: Sonya J
authors.initials: SJ
authors.lastname: McClure
authors.forename: Boris
authors.initials: B
authors.lastname: Sarcevic
authors.forename: Ross A
authors.initials: RA
authors.lastname: Boadle
authors.forename: Martin R
authors.initials: MR
authors.lastname: Larsen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cousin
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D034041:Monomeric Clathrin Assembly Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D011687:Purines / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000077546:Roscovitine; D012694:Serine / Q000378:metabolism; D012756:Sheep; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004791:Enzyme Inhibitors; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D011687:Purines; D011993:Recombinant Fusion Proteins; C439023:clathrin assembly protein AP180; D000077546:Roscovitine; C075637:amphiphysin; D012694:Serine; D051360:Cyclin-Dependent Kinase 5; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D034284:Dynamin I