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PMID:17128266

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Citation

Sieburth, D, Madison, JM and Kaplan, JM (2007) PKC-1 regulates secretion of neuropeptides. Nat. Neurosci. 10:49-57

Abstract

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.

Links

PubMed Online version:10.1038/nn1810

Keywords

Aldicarb/pharmacology; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins/physiology; 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/secretion; Patch-Clamp Techniques/methods; Protein Kinase C/physiology; Secretory Vesicles/drug effects; Secretory Vesicles/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:H9G2Y7

involved_in

GO:0040012: regulation of locomotion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:H9G2Y7

involved_in

GO:0007269: neurotransmitter secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:KPC1B

involved_in

GO:1990504: dense core granule exocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:KPC1B

involved_in

GO:0040012: regulation of locomotion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:KPC1B

involved_in

GO:0007269: neurotransmitter secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:KPC1B

involved_in

GO:0016079: synaptic vesicle exocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:KPC1B

located_in

GO:0043005: neuron projection

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:KPC1B

involved_in

GO:0007218: neuropeptide signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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