Phosphorylation of VAMP/synaptobrevin in synaptic vesicles by endogenous protein kinases

H. B. Nielander, F. Onofri, F. Valtorta, G. Schiavo, C. Montecucco, P. Greengard, F. Benfenati

Research output: Contribution to journalArticlepeer-review


VAMP/synaptobrevin (SYB), an integral membrane protein of small synaptic vesicles, is specifically cleaved by tetanus neurotoxin and botulinum neurotoxins B, D, F, and G and is thought to play an important role in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. Potential phosphorylation sites for various kinases are present in SYB sequence. We have studied whether SYB is a substrate for protein kinases that are present in nerve terminals and known to modulate neurotransmitter release. SYB can be phosphorylated within the same vesicle by endogenous Ca2+/calmodulin-dependent protein kinase II (CaMKII) associated with synaptic vesicles. This phosphorylation reaction occurs rapidly and involves serine and threonine residues in the cytoplasmic region of SYB. Similarly to CaMKII, a casein kinase II (CasKII) activity copurifying with synaptic vesicles is able to phosphorylate SYB selectively on serine residues of the cytoplasmic region. This phosphorylation reaction is markedly stimulated by sphingosine, a sphingolipid known to activate CasKII and to inhibit CaMKII and protein kinase C. The results show that SYB is a potential substrate for protein kinases involved in the regulation of neurotransmitter release and open the possibility that phosphorylation of SYB plays a role in modulating the molecular interactions between synaptic vesicles and the presynaptic membrane.

Original languageEnglish
Pages (from-to)1712-1720
Number of pages9
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - 1995


  • Ca/calmodulin-dependent protein kinase II
  • Casein kinase II
  • Clostridial neurotoxins
  • Neurotransmitter release
  • Synaptic vesicles
  • VAMP/synaptobrevin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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