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 mammals. 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. 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. 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 disease. 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 approximately 30-fold, and functions synergistically with MEC-2 (a stomatin-like protein that regulates MEC-4(d)/MEC-10(d) channel activity) 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.

Touch sensitivity in Caenorhabditis elegans

“…Both proteins colocalize with MEC-4 puncta and coimmunoprecipitate with MEC-4 and other mechanoreceptor channel subunits [17,31,98]. While both MEC-2 and UNC-24 appear to be part of the touch receptor complex, the effects of their loss on mechanosensation differ.…”

“…Along the touch neuron process, MEC-4 localizes to discrete puncta where mechanosensory proteins are believed to exist as a complex (Fig. 1d) [17]. When expressed in heterologous systems, MEC-4 and MEC-10 coimmunoprecipitate with each other and with other putative mechanosensory channel subunits [17,31].…”

“…1d) [17]. When expressed in heterologous systems, MEC-4 and MEC-10 coimmunoprecipitate with each other and with other putative mechanosensory channel subunits [17,31]. In frog oocytes, expression of the mutant form of MEC-4 that produces degeneration, MEC4d, can induce an amiloride-sensitive sodium current.…”

“…MEC-6 coimmunoprecipitates with the degenerins and other channel subunits [17], and mutations in mec-6 produce touch insensitivity [12], eliminate MEC-4 puncta [17] and suppress mec-4(d)-and mec-10(d)-induced degeneration [16,38]. Additionally, MEC-6 increases MEC-4d currents expressed in frog oocytes [17]. These results suggest that MEC-6 is a subunit of the mechanosensory complex required for proper channel localization, formation, and function.…”

Hepatitis B virus X protein targets the Bcl-2 protein CED-9 to induce intracellular Ca 2+ increase and cell death in Caenorhabditis elegans

“…1A, arrows). To determine the nature of HBx-induced cell death, we introduced the P hsp HBx transgenes into animals defective in ced-3, which encodes a caspase essential for apoptosis (21), or animals defective in mec-6, which is important for necrosis (22). A strong loss-offunction (lf) mutation in ced-3 (n2433) or mec-6 (e1342) partially suppressed embryonic lethality caused by HBx overexpression (Fig.…”