Pore-lining residues of MEC-4 and MEC-10 channel subunits tune the Caenorhabditis elegans degenerin channel's response to shear stress

The Journal of Biological Chemistry
Shujie ShiThomas R Kleyman

Abstract

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. We found that introducing mutations within the TM2 of MEC-4 or MEC-10 not only altered channel activity, but also affected the channel's response to LSS. This response was enhanced by Cys substitutions at selected MEC-4 sites (Phe715, Gly716, Gln718, and Leu719) between the degenerin and the putative amiloride-binding sites in this subunit. In contrast, the LSS response was largely blunted in MEC-10 variants bearing single Cys substitutions in the regions preceding and following the amiloride-binding site (Gly677-Leu681), as well as with four MEC-10 touch-deficient mutations that introduced charged residues into the TM2 domain. An enhanced response to LSS was observed with a MEC-10 mutation in the putative selectivity filter. Overal...Continue Reading

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Citations

Jan 28, 2020·American Journal of Physiology. Renal Physiology·Marcelo D Carattino, Nicolas Montalbetti

Related Concepts

MEC-10 protein, C elegans
Deg-1 protein, C elegans
Mec-4 protein, C elegans
Metazoa
Cell Surface Proteins
Oocytes
Protein Conformation
Stress, Mechanical
Xenopus laevis
Mutagenesis, Site-Directed

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