RT Journal Article
SR Electronic
T1 Mechanical activation of epithelial Na<sup>+</sup> channel relies on an interdependent activity of the extracellular matrix and extracellular <em>N</em>-glycans of αENaC
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 102756
DO 10.1101/102756
A1 Fenja Knoepp
A1 Zoe Ashley
A1 Daniel Barth
A1 Marina Kazantseva
A1 Pawel P. Szczesniak
A1 Wolfgang G. Clauss
A1 Mike Althaus
A1 Diego Alvarez de la Rosa
A1 Martin Fronius
YR 2017
UL http://biorxiv.org/content/early/2017/01/24/102756.abstract
AB Mechanotransduction describes how cells perceive their mechanical environment and mechanosensitive ion channels are important for this process. ENaC (epithelial Na+ channel)/DEG (degenerin) proteins form mechanosensitive ion channels and it is hypothesized their interaction with the extracellular matrix (ECM) via ‘tethers’ is required for mechanotransduction. Channels formed by vertebrate α, β and γ ENaC proteins are activated by shear force (SF) and mediate electrolyte/fluid-homeostasis and blood pressure regulation. Here, we report an interdependent activity of ENaC and the ECM that mediates SF effects in murine arteries and heterologously expressed channels. Furthermore, replacement of conserved extracellular N-glycosylated asparagines of αENaC decreased the SF response indicating that the attached N-glycans provide a connection to the ECM. Insertion of N-glycosylation sites into a channel subunit, innately lacking these motifs, increased its SF response. These experiments confirm an interdependent channel/ECM activity of mechanosensitive ENaC channel and highlight the role of channel N-glycans as new constituents for the translation of mechanical force into cellular signals.