RT Journal Article
SR Electronic
T1 ERRα coordinates actin and focal adhesion dynamics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.22.216085
DO 10.1101/2020.07.22.216085
A1 Tribollet, Violaine
A1 Cerutti, Catherine
A1 Géloën, Alain
A1 Danty-Berger, Emmanuelle
A1 De Mets, Richard
A1 Balland, Martial
A1 Courchet, Julien
A1 Vanacker, Jean-Marc
A1 Forcet, Christelle
YR 2020
UL http://biorxiv.org/content/early/2020/07/23/2020.07.22.216085.abstract
AB Cell migration depends on the dynamic organization of the actin cytoskeleton and assembly and disassembly of focal adhesions (FA). However the precise mechanisms coordinating these processes remain poorly understood. We previously identified the estrogen-related receptor α (ERRα) as a major regulator of cell migration. Here, we show that loss of ERRα leads to abnormal accumulation of actin filaments that is associated with an increase in the level of inactive form of the actin-depolymerizing factor cofilin. We further show that ERRα depletion decreases cell adhesion and promotes defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerization defects resulting from ERRα silencing, but not cell adhesion. Instead we found that MAP4K4 is a direct target of ERRα and down-regulation of its activity rescues cell adhesion and FA formation in the ERRα-depleted cells. Altogether, our results highlight a crucial role of ERRα in coordinating the dynamic of actin network and focal adhesion through the independent regulation of the RhoA and MAP4K4 pathways.Competing Interest StatementThe authors have declared no competing interest.