PKC-1 regulates secretion of neuropeptides.
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.
Sieburth
Derek
D
Department of Molecular Biology, Simches 7, Massachusetts General Hospital, 185 Cambridge St., Boston, Massachusetts 02114, USA.
Madison
Jon M
JM
Kaplan
Joshua M
JM
D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002352:Carrier Proteins; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003001:Cloning, Molecular / Q000379:methods; D003952:Diagnostic Imaging / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005089:Exocytosis / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D050505:Mutant Proteins / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011493:Protein Kinase C / Q000502:physiology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002800:Cholinesterase Inhibitors; D050505:Mutant Proteins; D009479:Neuropeptides; C083141:phorbol ester binding protein; D049452:Green Fluorescent Proteins; D000448:Aldicarb; D011493:Protein Kinase C