Phosphorylation of synaptic vesicle proteins: Modulation of the αSNAP interaction with the core complex

Abstract

We analyzed whether synaptic membrane trafficking proteins are substrates for casein kinase II, calcium/calmodulin-dependent protein kinase II, and cAMP-dependent protein kinase (PKA), three kinases implicated in the modulation of synaptic transmission. Each kinase phosphorylates a specific set of the vesicle proteins syntaxin 1A, N-ethylmaleimide-sensitive factor (NSF), vesicle-associated membrane protein (VAMP), synaptosome-associated 25- kDa protein (SNAP-25), n-sec1, α soluble NSF attachment protein (αSNAP), and synaptotagmin. VAMP is phosphorylated by calcium/calmodulin-dependent protein kinase II on serine 61. αSNAP is phosphorylated by PKA; however, the βSNAP isoform is phosphorylated only 20% as efficiently. αSNAP phosphorylated by pKA binds to the core docking and fusion complex 10 times weaker than the dephosphorylated form. These studies provide a first glimpse at regulatory events that may he important in modulating neurotransmitter release during learning and memory.