Affordable Access

Access to the full text

K + Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca 2+ Signaling and Rac1 Activity

Authors
  • Canales, Jimena1, 2
  • Cruz, Pablo1, 2
  • Díaz, Nicolás1, 2
  • Riquelme, Denise3
  • Leiva-Salcedo, Elías3
  • Cerda, Oscar1, 2, 4
  • 1 (N.D.)
  • 2 Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Universidad de Chile, 8380453 Santiago, Chile
  • 3 (E.L.-S.)
  • 4 The Wound Repair Treatment and Healing (WoRTH) Initiative, 8380453 Santiago, Chile
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Oct 12, 2020
Volume
9
Issue
10
Identifiers
DOI: 10.3390/cells9102273
PMID: 33053687
PMCID: PMC7600296
Source
PubMed Central
Keywords
License
Green

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.

Report this publication

Statistics

Seen <100 times