Phosphorylation of synaptic vesicle proteins: modulation of the alpha SNAP interaction with the core complex.

  • Hirling H
  • Scheller R
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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, alpha soluble NSF attachment protein (alpha SNAP), and synaptotagmin. VAMP is phosphorylated by calcium/calmodulin-dependent protein kinase II on serine 61. alpha SNAP is phosphorylated by PKA; however, the beta SNAP isoform is phosphorylated only 20% as efficiently. alpha SNAP 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 be important in modulating neurotransmitter release during learning and memory.

Author-supplied keywords

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases: meta
  • Carrier Proteins
  • Carrier Proteins: metabolism
  • Casein Kinase II
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic AMP-Dependent Protein Kinases: metabolism
  • Learning
  • Membrane Fusion
  • Membrane Proteins
  • Membrane Proteins: metabolism
  • Memory
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins
  • Phosphorylation
  • Phosphoserine
  • Protein-Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases: metabolism
  • R-SNARE Proteins
  • Recombinant Fusion Proteins
  • Recombinant Fusion Proteins: metabolism
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachme
  • Substrate Specificity
  • Synaptic Membranes
  • Synaptic Membranes: metabolism
  • Synaptic Vesicles
  • Synaptic Vesicles: metabolism
  • Synaptosomal-Associated Protein 25
  • Vesicular Transport Proteins

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Authors

  • H Hirling

  • R H Scheller

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