A zyxin-mediated mechanism for actin stress fiber maintenance and repair.
To maintain mechanical homeostasis, cells must recognize and respond to changes in cytoskeletal integrity. By imaging live cells expressing fluorescently tagged cytoskeletal proteins, we observed that actin stress fibers undergo local, acute, force-induced elongation and thinning events that compromise their stress transmission function, followed by stress fiber repair that restores this capability. The LIM protein zyxin rapidly accumulates at sites of strain-induced stress fiber damage and is essential for stress fiber repair and generation of traction force. Zyxin promotes recruitment of the actin regulatory proteins α-actinin and VASP to compromised stress fiber zones. α-Actinin plays a critical role in restoration of actin integrity at sites of local stress fiber damage, whereas both α-actinin and VASP independently contribute to limiting stress fiber elongation at strain sites, thus promoting stabilization of the stress fiber. Our findings demonstrate a mechanism for rapid repair and maintenance of the structural integrity of the actin cytoskeleton.
Smith
Mark A
MA
Department of Biology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Blankman
Elizabeth
E
Gardel
Margaret L
ML
Luettjohann
Laura
L
Waterman
Clare M
CM
Beckerle
Mary C
MC
D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D008667:Metalloproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D022502:Stress Fibers / Q000502:physiology*; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015815:Cell Adhesion Molecules; D008667:Metalloproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C498285:Zyx protein, mouse; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D000185:Actinin