ERRα coordinates actin and focal adhesion dynamics

Violaine Tribollet (1) , Catherine Cerutti (1) , Alain Géloën (2) , Emmanuelle Berger (2) , Richard de Mets (3) , Martial Balland (4) , Julien Courchet (5) , Jean-Marc Vanacker (1) , Christelle Forcet (1)

1 IGFL - Institut de Génomique Fonctionnelle de Lyon
2 LEM - Laboratoire d'Ecologie Microbienne - UMR 5557
3 NUS - National University of Singapore
4 LIPhy - Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères]
5 PGNM - Pathophysiologie et génétique du neurone et du muscle

Cell migration depends on the dynamic organisation of the actin cytoskeleton and assembly and disassembly of focal adhesions (FAs). However, the precise mechanisms coordinating these processes remain poorly understood. We previously identified the oestrogen-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 increased level of inactive form of the actin-depolymerising factor cofilin. We further show that ERRα depletion decreases cell adhesion and results in defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerisation 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 FAs through the independent regulation of the RhoA and MAP4K4 pathways.

Domaines: Organisation et fonctions cellulaires [q-bio.SC]; Cancer

Violaine Tribollet, Catherine Cerutti, Alain Géloën, Emmanuelle Berger, Richard de Mets, et al.. ERRα coordinates actin and focal adhesion dynamics. Cancer Gene Therapy, 2022, 29 (10), pp.1429-1438. ⟨10.1038/s41417-022-00461-6⟩. ⟨hal-04176612⟩