LIM domain proteins localize to strained actin, focal adhesions and adherens junctions in a tension-dependent manner

The actomyosin is coupled to mechanosensitive adhesion components such as focal adhesions (FAs) and adherens junctions (AJs), and can generate forces that maintain overall tissue homeostasis. A ubiquitous LIM (Lin11, Isl- 1, and Mec-3) domain family of proteins is associated with actomyosin and adhesions; for e.g., LIM protein Zyxin localizes to FAs, and is also seen at stress fiber strain sites (SFSS). The mechanisms by which LIM proteins sense forces and bind to strained actin or adhesive structures remain unknown. Here, we show that several members of the LIM family including Zyxin, Paxillin, FHL-2 and LIMD1 bind to SFs, FAs or AJs in a contractility-dependent manner. Specifically, the LIM regions of 18 different LIM proteins localize to SFSS. Similarly, paxillin-like 1 (Pxl1) protein from fission yeast also binds to strained actin in mammalian cells. This suggests an evolutionarily conserved mechanism by which the LIM domains recognize and bind to SFs or adhesive structures upon mechanical stress. We hypothesize that the force-sensitivity of LIM proteins could arise from the organization of the LIM region, amino acid substitutions, or post-translational modifications within the LIM region. We are currently exploring the molecular and mechanotransductive mechanisms by which the different LIM proteins sense mechanical stress and are recruited to distinct cellular structures. We are also investigating the effects of this force-sensitive recruitment of LIM proteins on downstream cellular processes.