PT  - JOURNAL ARTICLE
AU  - Violaine Tribollet
AU  - Catherine Cerutti
AU  - Alain Géloën
AU  - Emmanuelle Danty-Berger
AU  - Richard De Mets
AU  - Martial Balland
AU  - Julien Courchet
AU  - Jean-Marc Vanacker
AU  - Christelle Forcet
TI  - ERRα coordinates actin and focal adhesion dynamics
AID  - 10.1101/2020.07.22.216085
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.22.216085
4099  - http://biorxiv.org/content/early/2020/07/23/2020.07.22.216085.short
4100  - http://biorxiv.org/content/early/2020/07/23/2020.07.22.216085.full
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.