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PKC-1 regulates secretion of neuropeptides

Nature Neuroscience volume 10, pages 4957 (2007) | Download Citation

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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 η and ε 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.

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Change history

  • 10 December 2006

    Affiliation changed for two authors

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Acknowledgements

We thank the C. elegans stock center for strains, and I. Mori and Y. Okochi for nj3 mutants, for pYOS49 and for sharing unpublished results. We thank members of the Kaplan lab for advice and for critically reading the manuscript, Q. Ch'ng for reagents and for writing the coelomocyte fluorescence software and J. Dittman for developing punctal fluorescence analysis software. This work was supported by postdoctoral fellowships from the Damon Runyon Cancer Research Foundation (D.S.), the US National Institutes of Health (1F32NS10310) and the American Cancer Society (PF-98-065-01-DDC) (J.M.) and by research grants from the US National Institutes of Health (J.K.).

Author information

Author notes

    • Derek Sieburth

    Present address: Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.

Affiliations

  1. Department of Molecular Biology, Simches 7, Massachusetts General Hospital, 185 Cambridge St., Boston, Massachusetts 02114, USA.

    • Derek Sieburth
    • , Jon M Madison
    •  & Joshua M Kaplan

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Joshua M Kaplan.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    To verify that ACh activated currents were cholinergic, d-Tubocurare, an acetylcholine receptor antagonist, was shown to block the response to pressure ejection of acetylcholine onto body wall muscles in both (a) wild type (n = 2) and (b) pkc-1(nj3) (n = 2).

  2. 2.

    Supplementary Fig. 2

    The aldicarb resistance of unc-31 CAPS mutants was not enhanced by either egl-3 PC2 or egl-21 CPE mutants.

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DOI

https://doi.org/10.1038/nn1810

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