TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility

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 bu...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0130540-e0130540
Main Authors: 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 S, Cerda, Oscar
Format: Article
Language:English
Subjects:
Actin
Actins - metabolism
Adhesion
Calcium - metabolism
Calcium influx
Calcium ions
Calcium signalling
Cations
Cell adhesion & migration
Cell Lineage
Cell Movement - genetics
Contractility
Cytoskeleton
Cytoskeleton - genetics
Cytoskeleton - metabolism
Dismantling
Divalent cations
Fibroblasts
Focal adhesion kinase
Focal Adhesion Protein-Tyrosine Kinases - genetics
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Focal Adhesions - genetics
Focal Adhesions - metabolism
Genes
Humans
Kinases
Mass spectrometry
Mass spectroscopy
Muscle Contraction - genetics
Muscle proteins
Neurobiology
Neurosciences
Oscillations
Phosphorylation
Physiology
Prostate cancer
Proteins
Proteomics
Transient receptor potential proteins
TRPM Cation Channels - genetics
TRPM Cation Channels - metabolism
Wound healing
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0130540