KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis

José Rivas, Nicolás Díaz, Ian Silva, Danna Morales, Boris Lavanderos, Alhejandra Álvarez, María Paz Saldías, Eduardo Pulgar, Pablo Cruz, Diego Maureira, Guillermo Flores, Alicia Colombo, Constanza Blanco, Héctor R. Contreras, Fabián Jaña, Ivan Gallegos, Miguel L. Concha, Ariela Vergara-Jaque, Horacio Poblete, Wendy GonzálezDiego Varela, James S. Trimmer, Mónica Cáceres, Oscar Cerda

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.

Original languageEnglish (US)
JournalFASEB Journal
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • cell migration
  • KCTD proteins
  • TRP channels

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Rivas, J., Díaz, N., Silva, I., Morales, D., Lavanderos, B., Álvarez, A., Saldías, M. P., Pulgar, E., Cruz, P., Maureira, D., Flores, G., Colombo, A., Blanco, C., Contreras, H. R., Jaña, F., Gallegos, I., Concha, M. L., Vergara-Jaque, A., Poblete, H., ... Cerda, O. (Accepted/In press). KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis. FASEB Journal. https://doi.org/10.1096/fj.201901195RRR