K+ Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca2+ Signaling and Rac1 Activity
Author
dc.contributor.author
Canales, Jimena
Author
dc.contributor.author
Cruz, Pablo
Author
dc.contributor.author
Villacura Díaz, Nicolás Esteban
Author
dc.contributor.author
Riquelme, Denise
Author
dc.contributor.author
Leiva Salcedo, Elias
Author
dc.contributor.author
Cerda Arancibia, Óscar
Admission date
dc.date.accessioned
2021-04-09T19:12:03Z
Available date
dc.date.available
2021-04-09T19:12:03Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Cells 2020, 9, 2273
es_ES
Identifier
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10.3390/cells9102273
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/179044
Abstract
dc.description.abstract
Cell migration is critical for several physiological and pathophysiological processes. It depends on the coordinated action of kinases, phosphatases, Rho-GTPases proteins, and Ca2+ signaling. Interestingly, ubiquitination events have emerged as regulatory elements of migration. Thus, the role of proteins involved in ubiquitination processes could be relevant to a complete understanding of pro-migratory mechanisms. KCTD5 is a member of Potassium Channel Tetramerization Domain (KCTD) proteins that have been proposed as a putative adaptor for Cullin3-E3 ubiquitin ligase and a novel regulatory protein of TRPM4 channels. Here, we study whether KCTD5 participates in cell migration-associated mechanisms, such as focal adhesion dynamics and cellular spreading. Our results show that KCTD5 CRISPR/Cas9- and shRNA-based depletion in B16-F10 cells promoted an increase in cell migration and cell spreading, and a decrease in the focal adhesion area, consistent with an increased focal adhesion disassembly rate. The expression of a dominant-negative mutant of Rho-GTPases Rac1 precluded the KCTD5 depletion-induced increase in cell spreading. Additionally, KCTD5 silencing decreased the serum-induced Ca2+ response, and the reversion of this with ionomycin abolished the KCTD5 knockdown-induced decrease in focal adhesion size. Together, these data suggest that KCTD5 acts as a regulator of cell migration by modulating cell spreading and focal adhesion dynamics through Rac1 activity and Ca2+ signaling, respectively.
es_ES
Patrocinador
dc.description.sponsorship
Agencia Nacional de Investigacion y Desarrollo (ANID)-FONDECYT
1160518
1200917
Iniciativa Cientifica Milenio (ANID, Chile)
ANID-FONDECYT
3180556
11180536
1181814
Universidad de Santiago de Chile fund
USA1899Vridei 021943LE-PAP 312
ANID
21180306
K+ Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca2+ Signaling and Rac1 Activity