The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals

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Abstract

Transformation of mechanical energy into ionic currents is essential for touch, hearing and nociception. Although DEG/ENaC proteins are believed to form sensory mechanotransduction channels, the evidence for this role remains indirect. By recording from C. elegans touch receptor neurons in vivo, we found that external force evokes rapidly activating mechanoreceptor currents (MRCs) carried mostly by Na+ and blocked by amiloride—characteristics consistent with direct mechanical gating of a DEG/ENaC channel. Like mammalian Pacinian corpuscles, these neurons depolarized with both positive and negative changes in external force but not with sustained force. Null mutations in the DEG/ENaC gene mec-4 and in the accessory ion channel subunit genes mec-2 and mec-6 eliminated MRCs. In contrast, the genetic elimination of touch neuron–specific microtubules reduced, but did not abolish, MRCs. Our findings link the application of external force to the activation of a molecularly defined metazoan sensory transduction channel.

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Figure 1: In vivo recording from wild-type C. elegans touch neurons.
Figure 2: MRCs increase in proportion to the applied stimulus.
Figure 3: MRCs are carried by Na+ ions and blocked by amiloride.
Figure 4: Nonstationary noise analysis of MRCs.
Figure 5: Null mutations in genes that disrupt touch sensation abolish MRCs but do not affect other ionic currents in PLM cells.
Figure 6: Mutations that disrupt touch sensation and reduce, but do not abolish, MRCs.

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Acknowledgements

We thank J. Cueva for electron microscopy and stereology measurements; A. Meshel for help devising the calibration method for stimulus probes; A. Kovach and S. Lockery for assistance; and R. Aldrich and D. Lenzi for comments on the manuscript. This research funded by a Howard Hughes Medical Institute predoctoral fellowship to R.O., National Institutes of Health grant GM20997 to M.C., and faculty fellowships from the Donald B. and Delia E. Baxter and Alfred P. Sloan Foundations to M.B.G.

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Correspondence to Martin Chalfie or Miriam B Goodman.

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Supplementary information

Supplementary Fig. 1

Behavioral touch sensitivity in wild type and mec-4 animals. Both e1339 and u316 show greater touch response rates for stimuli delivered to the tail than for those delivered to the head; the reason for this difference in sensitivity is unknown. Wild type and the null allele mec-4(u253) are shown for comparison. Between 25 and 61 animals were tested for each genotype. (PDF 99 kb)

Supplementary Table 1 (PDF 20 kb)

Supplementary Methods (PDF 38 kb)

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O'Hagan, R., Chalfie, M. & Goodman, M. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat Neurosci 8, 43–50 (2005) doi:10.1038/nn1362

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