1. Department of Biological Sciences, Columbia University, New York, New York 10027, USA
2. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5345, USA

Correspondence to: Martin Chalfie¹ Correspondence and requests for materials should be addressed to M.C. (e-mail: Email: mc21@columbia.edu).

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 cells^{2, 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 degenerins^{4, 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.