Force- and cell state–dependent recruitment of Piezo1 drives focal adhesion dynamics and calcium entry

Mingxi Yao, Ajay Tijore, Delfine Cheng, Jinyuan Vero Li, Anushya Hariharan, Boris Martinac, Guy Tran Van Nhieu, Charles D. Cox, Michael Sheetz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mechanosensing is an integral part of many physiological processes including stem cell differentiation, fibrosis, and cancer progression. Two major mechanosensing systems—focal adhesions and mechanosensitive ion channels—can convert mechanical features of the microenvironment into biochemical signals. We report here unexpectedly that the mechanosensitive calcium-permeable channel Piezo1, previously perceived to be diffusive on plasma membranes, binds to matrix adhesions in a force-dependent manner, promoting cell spreading, adhesion dynamics, and calcium entry in normal but not in most cancer cells tested except some glioblastoma lines. A linker domain in Piezo1 is needed for binding to adhesions, and overexpression of the domain blocks Piezo1 binding to adhesions, decreasing adhesion size and cell spread area. Thus, we suggest that Piezo1 is a previously unidentified component of focal adhesions in nontransformed cells that catalyzes adhesion maturation and growth through force-dependent calcium signaling, but this function is absent in most cancer cells.

Original languageEnglish (US)
Article numbereabo1461
JournalScience Advances
Volume8
Issue number45
DOIs
StatePublished - Nov 2022

ASJC Scopus subject areas

  • General

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