Membrane Biology
Pore-lining residues of MEC-4 and MEC-10 channel subunits tune the Caenorhabditis elegans degenerin channel's response to shear stress
The Caenorhabditis elegans MEC-4/MEC-10 channel mediates the worm's response to gentle body touch and is activated by laminar shear stress (LSS) when expressed in Xenopus oocytes. Substitutions at multiple sites within the second transmembrane domain (TM2) of MEC-4 or MEC-10 abolish the gentle touch response in worms, but the roles of these residues in mechanosensing are unclear. The present study therefore examined the role of specific MEC-4 and MEC-10 TM2 residues in the channel's response to LSS.Conserved cysteines in the finger domain of the epithelial Na+ channel α and γ subunits are proximal to the dynamic finger–thumb domain interface
The epithelial Na+ channel (ENaC) is a member of the ENaC/degenerin family of ion channels. In the structure of a related family member, the “thumb” domain’s base interacts with the pore, and its tip interacts with the divergent “finger” domain. Between the base and tip, the thumb domain is characterized by a conserved five-rung disulfide ladder holding together two anti-parallel α helices. The ENaC α and γ subunits’ finger domains harbor autoinhibitory tracts that can be proteolytically liberated to activate the channel and also host an ENaC-specific pair of cysteines.
