Synaptic vesicle-associated Ca²⁺/calmodulin-dependent protein kinase II is a binding protein for synapsin I

Abstract

SYNAPSIN I is a synaptic vesicle-associated phosphoprotein that is involved in the modulation of neurotransmitter release¹. Ca²⁺/calmodulin-dependent protein kinase II, which phosphory-lates two sites in the carboxy-terminal region of synapsin I, causes synapsin I to dissociate from synaptic vesicles² and increases nerotransmitter release^3,4. Conversely, the dephosphorylated form of synapsin I, but not the form phosphorylated by Ca²⁺/cal-modulin-dependent protein kinase II, inhibits neurotransmitter release^4–6. The amino-terminal region of synapsin I interacts with membrane phospholipids, whereas the C-terminal region binds to a protein component of synaptic vesicles^7,8. 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.