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.Fluid flow modulates electrical activity in cardiac hERG potassium channels
Fluid movement within the heart generates substantial shear forces, but the effect of this mechanical stress on the electrical activity of the human heart has not been examined. The fast component of the delayed rectifier potassium currents responsible for repolarization of the cardiac action potential, Ikr, is encoded by the human ether-a-go-go related gene (hERG) channel. Here, we exposed hERG1a channel–expressing HEK293T cells to lamiNAr shear stress (LSS) and observed that this mechanical stress increased the whole-cell current by 30–40%.Activation of the Caenorhabditis elegans Degenerin Channel by Shear Stress Requires the MEC-10 Subunit
Mechanotransduction in Caenorhabditis elegans touch receptor neurons is mediated by an ion channel formed by MEC-4, MEC-10, and accessory proteins. To define the role of these subunits in the channel's response to mechanical force, we expressed degenerin channels comprising MEC-4 and MEC-10 in Xenopus oocytes and examined their response to laminar shear stress (LSS). Shear stress evoked a rapid increase in whole cell currents in oocytes expressing degenerin channels as well as channels with a MEC-4 degenerin mutation (MEC-4d), suggesting that C.The Transmembrane Domains of β and IX Subunits Mediate the Localization of the Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane Domain
Background: Localization of the GP Ib-IX complex to the lipid domain is mediated by the β and IX subunits.Results: Mutations in β/IX TMDs inhibit GP Ib-IX localization to the lipid domain.Conclusion: Localization of the GP Ib-IX complex to the lipid domain is mediated by β/IX TMDs.Significance: The β/IX TMDs may be a novel therapeutic target.
