1. Molecular mapping of transmembrane mechanotransduction through the β1 integrin-CD98hc-TRPV4 axis.
- Author
-
Potla R, Hirano-Kobayashi M, Wu H, Chen H, Mammoto A, Matthews BD, and Ingber DE
- Subjects
- Cell Adhesion, Endothelial Cells metabolism, TRPV Cation Channels genetics, TRPV Cation Channels metabolism, Integrin beta1 genetics, Integrin beta1 metabolism, Mechanotransduction, Cellular
- Abstract
One of the most rapid (less than 4 ms) transmembrane cellular mechanotransduction events involves activation of transient receptor potential vanilloid 4 (TRPV4) ion channels by mechanical forces transmitted across cell surface β1 integrin receptors on endothelial cells, and the transmembrane solute carrier family 3 member 2 (herein denoted CD98hc, also known as SLC3A2) protein has been implicated in this response. Here, we show that β1 integrin, CD98hc and TRPV4 all tightly associate and colocalize in focal adhesions where mechanochemical conversion takes place. CD98hc knockdown inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis reveals that forces applied to β1 integrin must be transmitted from its cytoplasmic C terminus via the CD98hc cytoplasmic tail to the ankyrin repeat domain of TRPV4 in order to produce ultrarapid, force-induced channel activation within the focal adhesion., Competing Interests: Competing interestsD.E.I. holds equity in Emulate, Inc. and chairs its Advisory Board; he also holds multiple patents that are licensed to the company., (© 2020. Published by The Company of Biologists Ltd.)
- Published
- 2020
- Full Text
- View/download PDF