Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses

Carlos Pardo-Pastor, Fanny Rubio-Moscardo, Marina Vogel-González, Selma A. Serra, Alexandros Afthinos, Sanela Mrkonjic, Olivier Destaing, Juan F. Abenza, José M. Fernández-Fernández, Xavier Trepat, Corinne Albiges-Rizo, Konstantinos Konstantopoulos, Miguel A. Valverde

Research output: Contribution to journalArticle

Abstract

Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.

Original languageEnglish (US)
Pages (from-to)1925-1930
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number8
DOIs
StatePublished - Feb 20 2018

Keywords

  • Actin stress fibers
  • Calcium signaling
  • Cancer
  • Mechanotransduction
  • RhoA

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses'. Together they form a unique fingerprint.

  • Cite this

    Pardo-Pastor, C., Rubio-Moscardo, F., Vogel-González, M., Serra, S. A., Afthinos, A., Mrkonjic, S., Destaing, O., Abenza, J. F., Fernández-Fernández, J. M., Trepat, X., Albiges-Rizo, C., Konstantopoulos, K., & Valverde, M. A. (2018). Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. Proceedings of the National Academy of Sciences of the United States of America, 115(8), 1925-1930. https://doi.org/10.1073/pnas.1718177115