title: 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.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blankman
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Deakin
authors.forename: Laura M
authors.initials: LM
authors.lastname: Hoffman
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Jensen
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Turner
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle
mesh_terms: D000199:Actins / Q000737:chemistry*; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D051419:Paxillin / Q000737:chemistry*; D019000:Phosphotyrosine / Q000737:chemistry; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D013269:Stochastic Processes; D022502:Stress Fibers / Q000378:metabolism*; D060589:Zyxin / Q000737:chemistry*
chemical_list: D000199:Actins; D051419:Paxillin; D060589:Zyxin; D049452:Green Fluorescent Proteins; D019000:Phosphotyrosine; D000205:Actomyosin; D051416:Focal Adhesion Protein-Tyrosine Kinases