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

A Corrigendum to this article was published on 20 June 2002

Abstract

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.

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Acknowledgements

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). https://doi.org/10.1038/4151039a

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