Cdk5 is essential for synaptic vesicle endocytosis.
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.
Tan
Timothy C
TC
Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
Valova
Valentina A
VA
Malladi
Chandra S
CS
Graham
Mark E
ME
Berven
Leise A
LA
Jupp
Orla J
OJ
Hansra
Gurdip
G
McClure
Sonya J
SJ
Sarcevic
Boris
B
Boadle
Ross A
RA
Larsen
Martin R
MR
Cousin
Michael A
MA
Robinson
Phillip J
PJ
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
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