Phosphorylation of a synaptic vesicle-associated protein by an inositol hexakisphosphate-regulated protein kinase.
Despite the fact that inositol hexakisphosphate (InsP(6)) is the most abundant inositol metabolite in cells, its cellular function has remained an enigma. In the present study, we present the first evidence of a protein kinase identified in rat cerebral cortex/hippocampus that is activated by InsP(6). The substrate for the InsP(6)-regulated protein kinase was found to be the synaptic vesicle-associated protein, pacsin/syndapin I. This brain-specific protein, which is highly enriched at nerve terminals, is proposed to act as a molecular link coupling components of the synaptic vesicle endocytic machinery to the cytoskeleton. We show here that the association between pacsin/syndapin I and dynamin I can be increased by InsP(6)-dependent phosphorylation of pacsin/syndapin I. These data provide a model by which InsP(6)-dependent phosphorylation regulates synaptic vesicle recycling by increasing the interaction between endocytic proteins at the synapse.
Department of Cell Physiology and Pharmacology, University of Leicester, Medical Sciences Building, University Road, Leicester, LE1 9HN, United Kingdom.
J M
JM
Hilton
M
M
Plomann
B
B
Ritter
J
J
Modregger
H N
HN
Freeman
J R
JR
Falck
U M
UM
Krishna
A B
AB
Tobin
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D010833:Phytic Acid; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C117738:Pacsin1 protein, rat; D011993:Recombinant Fusion Proteins; D010833:Phytic Acid; D011494:Protein Kinases; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins