MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation

  • A Corrigendum to this article was published on 20 June 2002


Touch sensitivity in animals relies on nerve endings in the skin that convert mechanical force into electrical signals. In the nematode Caenorhabditis elegans, gentle touch to the body wall is sensed by six mechanosensory neurons1 that express two amiloride-sensitive Na+ channel proteins (DEG/ENaC). These proteins, MEC-4 and MEC-10, are required for touch sensation and can mutate to cause neuronal degeneration2,3. Here we show that these mutant or ‘d’ forms of MEC-4 and MEC-10 produce a constitutively active, amiloride-sensitive ionic current when co-expressed in Xenopus oocytes, but not on their own. MEC-2, a stomatin-related protein needed for touch sensitivity4, increased the activity of mutant channels about 40-fold and allowed currents to be detected with wild-type MEC-4 and MEC-10. Whereas neither the central, stomatin-like domain of MEC-2 nor human stomatin retained the activity of full-length MEC-2, both produced amiloride-sensitive currents with MEC-4d. Our findings indicate that MEC-2 regulates MEC-4/MEC-10 ion channels and raise the possibility that similar ion channels may be formed by stomatin-like proteins and DEG/ENaC proteins that are co-expressed in both vertebrates and invertebrates5,6,7,8. Some of these channels may mediate mechanosensory responses.

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Figure 1: MEC-4d, MEC-10d, and MEC-2 produce amiloride-sensitive currents.
Figure 2: Functional interactions of MEC-4, MEC-10 and MEC-2.
Figure 3: MEC-2 interacts with MEC-4d and MEC-10d without altering surface expression.
Figure 4: Three domains are needed for full MEC-2 function.


  1. 1

    Chalfie, M. & Sulston, J. Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev. Biol. 82, 358–370 (1981).

    CAS  Article  Google Scholar 

  2. 2

    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 349, 588–593 (1991).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Huang, M. & Chalfie, M. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature 367, 467–470 (1994).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Huang, M., Gu, G., Ferguson, E. L. & Chalfie, M. A stomatin-like protein necessary for mechanosensation in C. elegans. Nature 378, 292–295 (1995).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Fricke, B. et al. Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons. Cell Tissue Res. 299, 327–334 (2000).

    CAS  PubMed  Google Scholar 

  6. 6

    Mannsfeldt, A. G., Carroll, P., Stucky, C. L. & Lewin, G. R. Stomatin, a MEC-2 like protein, is expressed by mammalian sensory neurons. Mol. Cell Neurosci. 13, 391–404 (1999).

    CAS  Article  Google Scholar 

  7. 7

    Tavernarakis, N., Shreffler, W., Wang, S. & Driscol, M. unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically gated channel that modulates C. elegans locomotion. Neuron 18, 107–119 (1997).

    CAS  Article  Google Scholar 

  8. 8

    Sedensky, M. M., Siefker, J. M. & Morgan, P. G. Model organisms: new insights into ion channel and transporter function. Stomatin homologues interact in Caenorhabditis elegans. Am. J. Physiol. Cell Physiol. 280, C1340–C1348 (2001).

    CAS  Article  Google Scholar 

  9. 9

    Chalfie, M. & Au, M. Genetic control of differentiation of the Caenorhabditis elegans touch receptor neurons. Science 243, 1027–1033 (1989).

    ADS  CAS  Article  Google Scholar 

  10. 10

    García-Añoveros, J., Garcia, J. A., Liu, J. D. & Corey, D. P. The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations. Neurons 20, 1231–1241 (1998).

    Article  Google Scholar 

  11. 11

    Adams, C. M. et al. Ripped pocket and pickpocket, novel Drosophila DEG/ENaC subunits expressed in early development and in mechanosensory neurons. J. Cell Biol. 140, 143–152 (1998).

    CAS  Article  Google Scholar 

  12. 12

    Waldmann, R., Champigny, G., Voilley, N., Lauritzen, I. & Lazdunski, M. The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J. Biol. Chem. 271, 10433–10436 (1996).

    CAS  Article  Google Scholar 

  13. 13

    Canessa, C. M. et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367, 463–467 (1994).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Rajaram, S., Spangler, T. L., Sedensky, M. M. & Morgan, P. G. A stomatin and a degenerin interact to control anesthetic sensitivity in Caenorhabditis elegans. Genetics 153, 1673–1682 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Palmer, L. G. Interactions of amiloride and other blocking cations with the apical Na channel in the toad urinary bladder. J. Membr. Biol. 87, 191–199 (1985).

    CAS  Article  Google Scholar 

  16. 16

    McNicholas, C. M. & Canessa, C. M. Diversity of channels generated by different combinations of epithelial sodium channel subunits. J. Gen. Physiol. 109, 681–692 (1997).

    CAS  Article  Google Scholar 

  17. 17

    Gu, G., Caldwell, G. A. & Chalfie, M. Genetic interactions affecting touch sensitivity in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 93, 6577–6582 (1996).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Muller, A. H., Gawantka, V., Ding, X. & Hausen, P. Maturation induced internalization of beta 1-integrin by Xenopus oocytes and formation of the maternal integrin pool. Mech. Dev. 42, 77–88 (1993).

    CAS  Article  Google Scholar 

  19. 19

    Lande, W. M., Thiemann, P. V. & Mentzer, W. C. Jr Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. J. Clin. Invest. 70, 1273–1280 (1982).

    CAS  Article  Google Scholar 

  20. 20

    Huang, M. Mechanosensory genes in Caenorhabditis elegans. PhD thesis, Columbia Univ. (1995).

  21. 21

    Snyers, L., Umlauf, E. & Prohaska, R. Oligomeric nature of the integral membrane protein stomatin. J. Biol. Chem. 273, 17221–17226 (1998).

    CAS  Article  Google Scholar 

  22. 22

    Snyers, L., Umlaug, E. & Prohaska, R. Cysteine 29 is the major palmitoylation site on stomatin. FEBS Lett. 449, 101–104 (1999).

    CAS  Article  Google Scholar 

  23. 23

    Salzer, U. & Prohaska, R. Stomatin, flotillin-1, and flotillin-2 are major integral proteins of erythrocyte lipid rafts. Blood 97, 1141–1143 (2001).

    CAS  Article  Google Scholar 

  24. 24

    García-Añoveros, J., Samad, T. A., Woolf, C. J. & Corey, D. P. Transport and localization of the DEG/ENaC ion channel BNaCl α to peripheral mechanosensory terminals of dorsal root ganglia neurons. J. Neurosci. 21, 2678–2686 (2001).

    Article  Google Scholar 

  25. 25

    Price, M. P. et al. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407, 1007–1011 (2000).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Lai, C. C., Hong, K., Kinnell, M., Chalfie, M. & Driscoll, M. Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans. J. Cell Biol. 133, 1071–1081 (1996).

    CAS  Article  Google Scholar 

  27. 27

    Kleckner, N., Bender, J. & Gottesman, S. Uses of transposons with emphasis on Tn10. Methods Enzymol. 204, 139–180 (1991).

    CAS  Article  Google Scholar 

  28. 28

    Hille, B. Ion Channels of Excitable Membranes. (Sinauer, Sunderland, Massachussetts, 2001).

    Google Scholar 

  29. 29

    Chillaron, J. et al. An intracellular trafficking defect in type I cystinuria rBAT mutants M467T and M467K. J. Biol. Chem. 272, 9543–9549 (1997).

    CAS  Article  Google Scholar 

  30. 30

    Woodhull, A. M. Ionic blockage of sodium channels in nerve. J. Gen. Physiol. 61, 687–708 (1973).

    CAS  Article  Google Scholar 

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We thank S. Zhang for polyclonal anti-MEC-2(145–481); M. Driscoll for wild-type degenerin cDNAs; G. Stewart for hStomatin cDNA; S. Hollman for pSGEM (a derivative of pGEM-HE); the Developmental Studies Hybridoma Bank for monoclonal antibodies against Xenopus β-integrin; J. Art, S. Firestein and J. Yang for the loan of equipment. We also thank L. Chen for technical assistance and T. Lu and J. Yang for assistance with preliminary experiments. This work was supported by a research grant from the National Institute of General Medical Sciences, NIH (M.C.), a Human Frontiers Science Program postdoctoral fellowship (D.S.C.), and an NRSA postdoctoral fellowship from the National Institute of Deafness and Other Communication Disorders, NIH (M.B.G.)

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Correspondence to Martin Chalfie.

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Goodman, M., Ernstrom, G., Chelur, D. et al. MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation. Nature 415, 1039–1042 (2002).

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