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

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 neurons 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 degeneration. 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 sensitivity, 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 invertebrates. Some of these channels may mediate mechanosensory responses.

Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain

“…Vol. 63,2006 Research Article 345 Figure 1. Conservation of amino acid sequences among metazoan reggie-1 and -2 genes.…”

“…Gaps are denoted by -and unknown sequences by · . 63.3% between vertebrate and invertebrate reggies/flotillins, over an ~428-aa-long polypeptide. Beyond metazoan taxa (supplementary table 1), unambiguous assignment of homology was not possible due to the low sequence similarity scores among the matches (below 26%).…”

“…Interestingly, all known SPFH family members (even those in bacteria [44], are involved in the scaffolding of specific DRMs, and exert their functions by forming platforms for the assembly of a specific set of proteins involved in signal transduction. For example, the three proteins neph, nephrin and podocin form microdomains in the slit diaphragm of the kidney [62]; prion proteins and other GPI-anchored proteins assemble in reggie/flotillin microdomains [6], and mechanosensory ion channels function within stomatin microdomains [63]. Even unrelated proteins such as caveolins perform comparable scaffolding functions in analogous caveolae DRM structures [64].…”

Touch sensitivity in Caenorhabditis elegans

“…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.…”

Temperature sensing across species

“…Members of the degenerin family of epithelial sodium channels (DEG/ENaC) are involved in many aspects of sensory signaling, including mechanosensory responses in the touch cells of C. elegans, responses in mammalian mechanoreceptors, salt and sour taste in mice, and proton responses in sensory afferents [113][114][115][116]. In regard to thermosensory signaling, in vitro recordings find that many of these channels are potentiated by cold temperatures [117].…”