Adhesion-derived condensates control component availability to regulate adhesion dynamics

Abstract

Abstract Integrin adhesion complexes mediate dynamic cell-matrix interactions to regulate cell adhesion, migration and invasion. While increasing evidence suggests that adhesion components can undergo liquid-liquid phase separation, the functional relevance of adhesion-derived condensates remains elusive. Here, we demonstrate that tensin 1 (TNS1), a multidomain adaptor protein linking active integrins with the actin cytoskeleton, forms condensates in cells to regulate adhesion component availability. We show that endogenous TNS1 condensates are formed upon focal adhesion disassembly or limited integrin-extracellular matrix engagement, acting as reversible reservoirs for unphosphorylated adhesion proteins. We identify the TNS1 intrinsically disordered region as governing TNS1 condensation and condensate biophysical properties. We further demonstrate a negative regulatory role for phosphorylation on condensate assembly upon stress-responsive kinase activation. Finally, we confirm the functional effects of TNS1 condensation on adhesion dynamics and cell migration, identifying a feedback loop acutely regulating kinase-mediated adhesion turnover upon integrin activation.