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The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel

Abstract

Mechanosensory transduction in touch receptor neurons is believed to be mediated by DEG/ENaC (degenerin/epithelial Na+ channel) proteins in nematodes and mammals1. In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells2,3. This phenotype is completely suppressed by mutation in a third gene, mec-6 (refs 3, 4), that is needed for touch sensitivity. This last gene is also required for the function of other degenerins4,5,6,7,8. Here we show that mec-6 encodes a single-pass membrane-spanning protein with limited similarity to paraoxonases, which are implicated in human coronary heart disease9. This gene is expressed in muscle cells and in many neurons, including the six touch receptor neurons. MEC-6 increases amiloride-sensitive Na+ currents produced by MEC-4(d)/MEC-10(d) by 30-fold, and functions synergistically with MEC-2 (a stomatin-like protein10 that regulates MEC-4(d)/MEC-10(d) channel activity11) to increase the currents by 200-fold. MEC-6 physically interacts with all three channel proteins. In vivo, MEC-6 co-localizes with MEC-4, and is required for punctate MEC-4 expression along touch-neuron processes. We propose that MEC-6 is a part of the degenerin channel complex that may mediate mechanotransduction in touch cells.

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Figure 1: Characterization of mec-6.
Figure 2: Expression of MEC proteins in Xenopus oocytes.
Figure 3: Physical interaction among MEC-6, MEC-4, MEC-10 and MEC-2.
Figure 4: mec-6 co-localizes with MEC-4 in a punctuate pattern in the touch cells.

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Acknowledgements

We thank J. Kong for technical assistance in isolating mec-6 cDNAs. This work was supported by the National Institutes of Health (M.C.), a Human Frontiers Science Program postdoctoral fellowship (D.S.C.), and a postdoctoral fellowship from the National Institute of Deafness and other Communication Disorders (M.B.G.).

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Correspondence to Martin Chalfie.

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Chelur, D., Ernstrom, G., Goodman, M. et al. The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel. Nature 420, 669–673 (2002). https://doi.org/10.1038/nature01205

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