TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility

Mónica Cáceres, Liliana Ortiz, Tatiana Recabarren, Anibal Romero, Alicia Colombo, Elías Leiva-Salcedo, Diego Varela, José Rivas, Ian Silva, Diego Morales, Camilo Campusano, Oscar Almarza, Felipe Simon, Hector Toledo, Kang Sik Park, James Trimmer, Oscar Cerda

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca<sup>2+</sup> oscillations. TRPM4 is a Ca<sup>2+</sup>-activated non-selective cationic channel (Ca<sup>2+</sup>-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca<sup>2+</sup> influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility.

Original languageEnglish (US)
Article numbere0130540
JournalPLoS One
Issue number6
StatePublished - Jun 25 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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