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Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release

Academic Article
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Overview

authors

  • Maximov, Anton
  • Shin, O. H.
  • Liu, X. R.
  • Sudhof, T. C.

publication date

  • January 2007

journal

  • Journal of Cell Biology  Journal

abstract

  • Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca(2+). In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine(97), and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine(97) by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca(2+)-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.

subject areas

  • Amino Acid Sequence
  • Animals
  • Calcium
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Gene Expression Profiling
  • Glycosylation
  • Hippocampus
  • Inhibitory Postsynaptic Potentials
  • Mice
  • Molecular Sequence Data
  • Neurotransmitter Agents
  • Phospholipids
  • Phosphoproteins
  • Phosphorylation
  • Phosphoserine
  • Protein Binding
  • Protein Transport
  • Rats
  • Synaptic Vesicles
  • Synaptotagmin I
  • Synaptotagmins
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Identity

PubMed Central ID

  • PMC2063632

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200607021

PubMed ID

  • 17190793
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Additional Document Info

start page

  • 113

end page

  • 124

volume

  • 176

issue

  • 1

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