Focal adhesion-derived liquid-liquid phase separations regulate mRNA translation.
Abstract:
Liquid-liquid phase separation (LLPS) has emerged as a major organizing principle in cells.
Recent work showed that multiple components of integrin-mediated focal adhesions including
p130Cas can form LLPS, which govern adhesion dynamics and related cell behaviors. In this
study, we found that the focal adhesion protein p130Cas drives formation of structures with the
characteristics of LLPS that bud from focal adhesions into the cytoplasm. Condensing
concentrated cytoplasm around p130Cas-coated beads allowed their isolation, which were
enriched in a subset of focal adhesion proteins, mRNAs and RNA binding proteins, including
those implicated in inhibiting mRNA translation. Plating cells on very high concentrations of
fibronectin to induce large focal adhesions inhibited message translation which required
p130Cas and correlated with droplet formation. Photo-induction of p130Cas condensates using
the Cry2 system also reduced translation. These results identify a novel regulatory mechanism
in which high adhesion limits message translation via induction of p130Cas-dependent
cytoplasmic LLPS. This mechanism may contribute to the quiescent state of very strongly
adhesive myofibroblasts and senescent cells.
