Skip to main content
Genetics logoLink to Genetics
. 1995 Mar;139(3):1261–1272. doi: 10.1093/genetics/139.3.1261

The Unc-8 and Sup-40 Genes Regulate Ion Channel Function in Caenorhabditis Elegans Motorneurons

W Shreffler 1, T Magardino 1, K Shekdar 1, E Wolinsky 1
PMCID: PMC1206455  PMID: 7539392

Abstract

Two Caenorhabditis elegans genes, unc-8 and sup-40, have been newly identified, by genetic criteria, as regulating ion channel function in motorneurons. Two dominant unc-8 alleles cause motorneuron swelling similar to that of other neuronal types in dominant mutants of the deg-1 gene family, which is homologous to a mammalian gene family encoding amiloride-sensitive sodium channel subunits. As for previously identified deg-1 family members, unc-8 dominant mutations are recessively suppressed by mutations in the mec-6 gene, which probably encodes a second type of channel component. An unusual dominant mutation, sup-41 (lb125), also co-suppresses unc-8 and deg-1, suggesting the existence of yet another common component of ion channels containing unc-8 or deg-1 subunits. Dominant, transacting, intragenic suppressor mutations have been isolated for both unc-8 and deg-1, consistent with the idea that, like their mammalian homologues, the two gene products function as multimers. The sup-40 (lb130) mutation dominantly suppresses unc-8 motorneuron swelling and produces a novel swelling phenotype in hypodermal nuclei. sup-40 may encode an ion channel component or regulator that can correct the osmotic defect caused by abnormal unc-8 channels.

Full Text

The Full Text of this article is available as a PDF (5.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belardetti F., Campbell W. B., Falck J. R., Demontis G., Rosolowsky M. Products of heme-catalyzed transformation of the arachidonate derivative 12-HPETE open S-type K+ channels in Aplysia. Neuron. 1989 Oct;3(4):497–505. doi: 10.1016/0896-6273(89)90208-0. [DOI] [PubMed] [Google Scholar]
  2. Braha O., Edmonds B., Sacktor T., Kandel E. R., Klein M. The contributions of protein kinase A and protein kinase C to the actions of 5-HT on the L-type Ca2+ current of the sensory neurons in Aplysia. J Neurosci. 1993 May;13(5):1839–1851. doi: 10.1523/JNEUROSCI.13-05-01839.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Canessa C. M., Horisberger J. D., Rossier B. C. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature. 1993 Feb 4;361(6411):467–470. doi: 10.1038/361467a0. [DOI] [PubMed] [Google Scholar]
  4. Canessa C. M., Schild L., Buell G., Thorens B., Gautschi I., Horisberger J. D., Rossier B. C. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994 Feb 3;367(6462):463–467. doi: 10.1038/367463a0. [DOI] [PubMed] [Google Scholar]
  5. Chalfie M., Driscoll M., Huang M. Degenerin similarities. Nature. 1993 Feb 11;361(6412):504–504. doi: 10.1038/361504a0. [DOI] [PubMed] [Google Scholar]
  6. Chalfie M., Sulston J. E., White J. G., Southgate E., Thomson J. N., Brenner S. The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci. 1985 Apr;5(4):956–964. doi: 10.1523/JNEUROSCI.05-04-00956.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chalfie M., Wolinsky E. The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans. Nature. 1990 May 31;345(6274):410–416. doi: 10.1038/345410a0. [DOI] [PubMed] [Google Scholar]
  8. Collins J., Saari B., Anderson P. Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans. Nature. 1987 Aug 20;328(6132):726–728. doi: 10.1038/328726a0. [DOI] [PubMed] [Google Scholar]
  9. Covarrubias M., Wei A. A., Salkoff L. Shaker, Shal, Shab, and Shaw express independent K+ current systems. Neuron. 1991 Nov;7(5):763–773. doi: 10.1016/0896-6273(91)90279-9. [DOI] [PubMed] [Google Scholar]
  10. Desai C., Garriga G., McIntire S. L., Horvitz H. R. A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons. Nature. 1988 Dec 15;336(6200):638–646. doi: 10.1038/336638a0. [DOI] [PubMed] [Google Scholar]
  11. Driscoll M., Chalfie M. The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature. 1991 Feb 14;349(6310):588–593. doi: 10.1038/349588a0. [DOI] [PubMed] [Google Scholar]
  12. Franks N. P., Lieb W. R. Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607–614. doi: 10.1038/367607a0. [DOI] [PubMed] [Google Scholar]
  13. Hedgecock E. M., Thomson J. N. A gene required for nuclear and mitochondrial attachment in the nematode Caenorhabditis elegans. Cell. 1982 Aug;30(1):321–330. doi: 10.1016/0092-8674(82)90038-1. [DOI] [PubMed] [Google Scholar]
  14. Hong K., Driscoll M. A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans. Nature. 1994 Feb 3;367(6462):470–473. doi: 10.1038/367470a0. [DOI] [PubMed] [Google Scholar]
  15. Jiang C., Finkbeiner W. E., Widdicombe J. H., McCray P. B., Jr, Miller S. S. Altered fluid transport across airway epithelium in cystic fibrosis. Science. 1993 Oct 15;262(5132):424–427. doi: 10.1126/science.8211164. [DOI] [PubMed] [Google Scholar]
  16. Light D. B., Corbin J. D., Stanton B. A. Dual ion-channel regulation by cyclic GMP and cyclic GMP-dependent protein kinase. Nature. 1990 Mar 22;344(6264):336–339. doi: 10.1038/344336a0. [DOI] [PubMed] [Google Scholar]
  17. Lingueglia E., Renard S., Waldmann R., Voilley N., Champigny G., Plass H., Lazdunski M., Barbry P. Different homologous subunits of the amiloride-sensitive Na+ channel are differently regulated by aldosterone. J Biol Chem. 1994 May 13;269(19):13736–13739. [PubMed] [Google Scholar]
  18. Lingueglia E., Voilley N., Waldmann R., Lazdunski M., Barbry P. Expression cloning of an epithelial amiloride-sensitive Na+ channel. A new channel type with homologies to Caenorhabditis elegans degenerins. FEBS Lett. 1993 Feb 22;318(1):95–99. doi: 10.1016/0014-5793(93)81336-x. [DOI] [PubMed] [Google Scholar]
  19. Oberleithner H., Schuricht B., Wünsch S., Schneider S., Püschel B. Role of H+ ions in volume and voltage of epithelial cell nuclei. Pflugers Arch. 1993 Apr;423(1-2):88–96. doi: 10.1007/BF00374965. [DOI] [PubMed] [Google Scholar]
  20. Park E. C., Horvitz H. R. Mutations with dominant effects on the behavior and morphology of the nematode Caenorhabditis elegans. Genetics. 1986 Aug;113(4):821–852. doi: 10.1093/genetics/113.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ruppersberg J. P., Schröter K. H., Sakmann B., Stocker M., Sewing S., Pongs O. Heteromultimeric channels formed by rat brain potassium-channel proteins. Nature. 1990 Jun 7;345(6275):535–537. doi: 10.1038/345535a0. [DOI] [PubMed] [Google Scholar]
  22. Schacher S., Kandel E. R., Montarolo P. cAMP and arachidonic acid simulate long-term structural and functional changes produced by neurotransmitters in Aplysia sensory neurons. Neuron. 1993 Jun;10(6):1079–1088. doi: 10.1016/0896-6273(93)90056-w. [DOI] [PubMed] [Google Scholar]
  23. Schinkmann K., Li C. Localization of FMRFamide-like peptides in Caenorhabditis elegans. J Comp Neurol. 1992 Feb 8;316(2):251–260. doi: 10.1002/cne.903160209. [DOI] [PubMed] [Google Scholar]
  24. Sheng M., Liao Y. J., Jan Y. N., Jan L. Y. Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature. 1993 Sep 2;365(6441):72–75. doi: 10.1038/365072a0. [DOI] [PubMed] [Google Scholar]
  25. Smith J. J., Karp P. H., Welsh M. J. Defective fluid transport by cystic fibrosis airway epithelia. J Clin Invest. 1994 Mar;93(3):1307–1311. doi: 10.1172/JCI117087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith P. R., Benos D. J. Epithelial Na+ channels. Annu Rev Physiol. 1991;53:509–530. doi: 10.1146/annurev.ph.53.030191.002453. [DOI] [PubMed] [Google Scholar]
  27. Turnheim K. Intrinsic regulation of apical sodium entry in epithelia. Physiol Rev. 1991 Apr;71(2):429–445. doi: 10.1152/physrev.1991.71.2.429. [DOI] [PubMed] [Google Scholar]
  28. Welsh M. J., Smith A. E. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993 Jul 2;73(7):1251–1254. doi: 10.1016/0092-8674(93)90353-r. [DOI] [PubMed] [Google Scholar]
  29. Wünsch S., Schneider S., Schwab A., Oberleithner H. 20-OH-ecdysone swells nuclear volume by alkalinization in salivary glands of Drosophila melanogaster. Cell Tissue Res. 1993 Oct;274(1):145–151. doi: 10.1007/BF00327995. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES