LIM Domains Target Actin Regulators Paxillin and Zyxin to Sites of Stress Fiber Strain

Abstract

Contractile actomyosin stress fibers are critical for maintaining the force balance between the interior of the cell and its environment. Consequently, the actin cytoskeleton undergoes dynamic mechanical loading. This results in spontaneous, stochastic, highly localized strain events, characterized by thinning and elongation within a discrete region of stress fiber. Previous work showed the LIM-domain adaptor protein, zyxin, is essential for repair and stabilization of these sites. Using live imaging, we show paxillin, another LIM-domain adaptor protein, is also recruited to stress fiber strain sites. Paxillin recruitment to stress fiber strain sites precedes zyxin recruitment. Zyxin and paxillin are each recruited independently of the other. In cells lacking paxillin, actin recovery is abrogated, resulting in slowed actin recovery and increased incidence of catastrophic stress fiber breaks. For both paxillin and zyxin, the LIM domains are necessary and sufficient for recruitment. This work provides further evidence of the critical role of LIM-domain proteins in responding to mechanical stress in the actin cytoskeleton.

Emerging properties of adhesion complexes: what are they and what do they do?

“…Zyxin is a mechanosensitive core adhesome component that is recruited from adhesion complexes to actin stress fibres upon force application [71]. Importantly, zyxin translocates specifically to stochastic or force-induced strain sites, in a LIM domaindependent manner, where it recruits a-actinin and VASP to repair and stabilise damaged fibres [72,73]. Thus, zyxin controls cellular repair mechanisms in a manner that is independent of its role in adhesion complexes.…”

“…Paxillin, another LIM-domain-containing core adhesome component, can also be recruited to strain sites to initiate actin repair [72,74]. However, unlike zyxin, recruitment of paxillin to strain sites is not driven by cyclical stretch In addition, protein kinase C alpha (PKCa) and Rab21 can bind to b-integrins and control endocytosis.…”

LIM proteins in actin cytoskeleton mechanoresponse

“…Of these 26 proteins, the FA concentrations of 21 are sensitive to contractility inhibition [22, 23]. A subset of these proteins, zyxin, Hic-5, and CRP are recruited to SFs in response to stretch [21, 24], while zyxin and the adapter protein paxillin mediate strain induced SF repair [20, 25, 26]. These recent discoveries support the hypothesis that LIM proteins are mechanoresponders.…”

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

“…This supports an important role of zyxin in relaying signals from actin-rich cell adhesion sites to the nucleus. The LIM domain is sufficient to localize zyxin to actin stress fibers (Smith et al, 2013) and to the leading edge of migrating cells in response to force (Uemura et al, 2011) and is required for stretch-induced actin remodeling (Hoffman et al, 2012), thus also implicating zyxin in more local cytoskeletal remodeling. Notably, zyxin is often found to be enriched in epithelial and muscular tissues, but is expressed at relatively low levels in the nervous system (Macalma et al, 1996).…”