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 journalArticle

20 Citations (Scopus)

Abstract

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
Volume10
Issue number6
DOIs
StatePublished - Jun 25 2015

Fingerprint

Focal Adhesions
adhesion
Adhesion
calcium
cell movement
non-specific protein-tyrosine kinase
proteins
cytoskeleton
tissue repair
Focal Adhesion Protein-Tyrosine Kinases
microfilaments
cell adhesion
Proteins
proteomics
Divalent Cations
oscillation
cations
Cytoskeleton
Actin Cytoskeleton
Proteomics

ASJC Scopus subject areas

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

Cite this

Cáceres, M., Ortiz, L., Recabarren, T., Romero, A., Colombo, A., Leiva-Salcedo, E., ... Cerda, O. (2015). TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility. PLoS One, 10(6), [e0130540]. https://doi.org/10.1371/journal.pone.0130540

TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility. / Cáceres, Mónica; Ortiz, Liliana; Recabarren, Tatiana; Romero, Anibal; Colombo, Alicia; Leiva-Salcedo, Elías; Varela, Diego; Rivas, José; Silva, Ian; Morales, Diego; Campusano, Camilo; Almarza, Oscar; Simon, Felipe; Toledo, Hector; Park, Kang Sik; Trimmer, James; Cerda, Oscar.

In: PLoS One, Vol. 10, No. 6, e0130540, 25.06.2015.

Research output: Contribution to journalArticle

Cáceres, M, Ortiz, L, Recabarren, T, Romero, A, Colombo, A, Leiva-Salcedo, E, Varela, D, Rivas, J, Silva, I, Morales, D, Campusano, C, Almarza, O, Simon, F, Toledo, H, Park, KS, Trimmer, J & Cerda, O 2015, 'TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility', PLoS One, vol. 10, no. 6, e0130540. https://doi.org/10.1371/journal.pone.0130540
Cáceres M, Ortiz L, Recabarren T, Romero A, Colombo A, Leiva-Salcedo E et al. TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility. PLoS One. 2015 Jun 25;10(6). e0130540. https://doi.org/10.1371/journal.pone.0130540
Cáceres, Mónica ; Ortiz, Liliana ; Recabarren, Tatiana ; Romero, Anibal ; Colombo, Alicia ; Leiva-Salcedo, Elías ; Varela, Diego ; Rivas, José ; Silva, Ian ; Morales, Diego ; Campusano, Camilo ; Almarza, Oscar ; Simon, Felipe ; Toledo, Hector ; Park, Kang Sik ; Trimmer, James ; Cerda, Oscar. / TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility. In: PLoS One. 2015 ; Vol. 10, No. 6.
@article{d191b5b789394727862d87aa233bf4a6,
title = "TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility",
abstract = "Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-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 Ca2+ 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.",
author = "M{\'o}nica C{\'a}ceres and Liliana Ortiz and Tatiana Recabarren and Anibal Romero and Alicia Colombo and El{\'i}as Leiva-Salcedo and Diego Varela and Jos{\'e} Rivas and Ian Silva and Diego Morales and Camilo Campusano and Oscar Almarza and Felipe Simon and Hector Toledo and Park, {Kang Sik} and James Trimmer and Oscar Cerda",
year = "2015",
month = "6",
day = "25",
doi = "10.1371/journal.pone.0130540",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - TRPM4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility

AU - Cáceres, Mónica

AU - Ortiz, Liliana

AU - Recabarren, Tatiana

AU - Romero, Anibal

AU - Colombo, Alicia

AU - Leiva-Salcedo, Elías

AU - Varela, Diego

AU - Rivas, José

AU - Silva, Ian

AU - Morales, Diego

AU - Campusano, Camilo

AU - Almarza, Oscar

AU - Simon, Felipe

AU - Toledo, Hector

AU - Park, Kang Sik

AU - Trimmer, James

AU - Cerda, Oscar

PY - 2015/6/25

Y1 - 2015/6/25

N2 - Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-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 Ca2+ 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.

AB - Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-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 Ca2+ 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.

UR - http://www.scopus.com/inward/record.url?scp=84938630783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938630783&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0130540

DO - 10.1371/journal.pone.0130540

M3 - Article

C2 - 26110647

AN - SCOPUS:84938630783

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e0130540

ER -