Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I.
Synapsin I is a synaptic vesicle-associated phosphoprotein that is involved in the modulation of neurotransmitter release. Ca2+/calmodulin-dependent protein kinase II, which phosphorylates two sites in the carboxy-terminal region of synapsin I, causes synapsin I to dissociate from synaptic vesicles and increases neurotransmitter release. Conversely, the dephosphorylated form of synapsin I, but not the form phosphorylated by Ca2+/calmodulin-dependent protein kinase II, inhibits neurotransmitter release. The amino-terminal region of synapsin I interacts with membrane phospholipids, whereas the C-terminal region binds to a protein component of synaptic vesicles. Here we demonstrate that the binding of the C-terminal region of synapsin I involves the regulatory domain of a synaptic vesicle-associated form of Ca2+/calmodulin-dependent protein kinase II. Our results indicate that this form of the kinase functions both as a binding protein for synapsin I, and as an enzyme that phosphorylates synapsin I and promotes its dissociation from the vesicles.
Benfenati
F
F
Institute of Human Physiology, University of Modena, Italy.
Valtorta
F
F
Rubenstein
J L
JL
Gorelick
F S
FS
Greengard
P
P
Czernik
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013379:Substrate Specificity; D016704:Synapsins / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
D017981:Receptors, Neurotransmitter; D016704:Synapsins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases