“LIM Domain Proteins in Cell Mechanotransduction”

My lab studies the design principles of cytoskeletal materials the drive cellular morphogenesis, with a focus on contractile machinery in adherent cells. In addition to force generation, a key feature of these materials are distributed force sensors which allow for rapid assembly, adaptation, repair and disintegration. Here I will discuss our recent identification of 18 proteins from the zyxin, paxillin, Tes and Enigma families with mechanosensitive LIM (Lin11, Isl- 1 & Mec-3) domains. We developed a screen to assess the force-dependent localization of LIM domain-containing region (LCR) from ~30 genes to the actin cytoskeleton and identified features common to their force-sensitive localization. Through in vitro reconstitution, we found that the LCR binds directly to mechanically stressed actin filaments. Moreover, the LCR from the fission yeast protein paxillin-like 1 is also mechanosensitive, suggesting force-sensitivity is highly conserved. We speculate that the evolutionary emergence of contractile F-actin machinery coincided with, or required, proteins that could report on the stresses present there to maintain homeostasis of actively stressed networks.