PKC-1 regulates secretion of neuropeptides

Nat Neurosci. 2007 Jan;10(1):49-57. doi: 10.1038/nn1810. Epub 2006 Nov 26.


The secretion of neurotransmitters and neuropeptides is mediated by distinct organelles-synaptic vesicles (SVs) and dense-core vesicles (DCVs), respectively. Relatively little is known about the factors that differentially regulate SV and DCV secretion. Here we show that protein kinase C-1 (PKC-1), which is most similar to the vertebrate PKC eta and epsilon isoforms, regulates exocytosis of DCVs in Caenorhabditis elegans motor neurons. Mutants lacking PCK-1 activity had delayed paralysis induced by the acetylcholinesterase inhibitor aldicarb, whereas mutants with increased PKC-1 activity had more rapid aldicarb-induced paralysis. Imaging and electrophysiological assays indicated that SV release occurred normally in pkc-1 mutants. By contrast, genetic analysis of aldicarb responses and imaging of fluorescently tagged neuropeptides indicated that mutants lacking PKC-1 had reduced neuropeptide secretion. Similar neuropeptide secretion defects were found in mutants lacking unc-31 (encoding the protein CAPS) or unc-13 (encoding Munc13). These results suggest that PKC-1 selectively regulates DCV release from neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldicarb / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / physiology*
  • Carrier Proteins
  • Cholinesterase Inhibitors / pharmacology
  • Cloning, Molecular / methods
  • Diagnostic Imaging / methods
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Exocytosis / drug effects
  • Exocytosis / genetics
  • Gene Expression / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Muscles / drug effects
  • Muscles / metabolism
  • Mutant Proteins / physiology
  • Neuropeptides / metabolism*
  • Patch-Clamp Techniques / methods
  • Protein Kinase C / physiology*
  • Secretory Vesicles / drug effects
  • Secretory Vesicles / physiology


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cholinesterase Inhibitors
  • Mutant Proteins
  • Neuropeptides
  • phorbol ester binding protein
  • Green Fluorescent Proteins
  • Aldicarb
  • Protein Kinase C