TY - JOUR
T1 - The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction
AU - Chambliss, Allison B.
AU - Khatau, Shyam B.
AU - Erdenberger, Nicholas
AU - Robinson, D. Kyle
AU - Hodzic, Didier
AU - Longmore, Gregory D.
AU - Wirtz, Denis
N1 - Funding Information:
This work was supported by NIH grants R01GM084204 and U54CA143868, and a Research Grant from the Muscular Dystrophy Association (DH). ABC and SBK were supported by IGERT-NSF graduate fellowships. The authors thank Dr. Yungfeng Feng for providing focal adhesion protein knockdown cell lines. Publication of this article was funded in part by the Open Access Promotion Fund of the Johns Hopkins University Libraries.
PY - 2013/1/18
Y1 - 2013/1/18
N2 - Cells continuously sense and respond to external mechanical forces through their cytoskeleton. Here we show that only a small subset of actin fibers, those forming the perinuclear actin cap that wraps around the nucleus, form in response to low physiological mechanical stresses in adherent fibroblasts. While conventional basal stress fibers form only past a threshold shear stress of 0.5 dyn/cm2, actin-cap fibers are formed at shear stresses 50 times lower and orders-of-magnitude faster than biochemical stimulation. This fast differential response is uniquely mediated by focal adhesion protein zyxin at low shear stress and actomyosin fibers of the actin cap. We identify additional roles for lamin A/C of the nuclear lamina and linkers of nucleus to cytoskeleton (LINC) molecules nesprin2giant and nesprin3, which anchor actin cap fibers to the nucleus. These results suggest an interconnected physical pathway for mechanotransduction, from the extracellular milieu to the nucleus.
AB - Cells continuously sense and respond to external mechanical forces through their cytoskeleton. Here we show that only a small subset of actin fibers, those forming the perinuclear actin cap that wraps around the nucleus, form in response to low physiological mechanical stresses in adherent fibroblasts. While conventional basal stress fibers form only past a threshold shear stress of 0.5 dyn/cm2, actin-cap fibers are formed at shear stresses 50 times lower and orders-of-magnitude faster than biochemical stimulation. This fast differential response is uniquely mediated by focal adhesion protein zyxin at low shear stress and actomyosin fibers of the actin cap. We identify additional roles for lamin A/C of the nuclear lamina and linkers of nucleus to cytoskeleton (LINC) molecules nesprin2giant and nesprin3, which anchor actin cap fibers to the nucleus. These results suggest an interconnected physical pathway for mechanotransduction, from the extracellular milieu to the nucleus.
UR - http://www.scopus.com/inward/record.url?scp=84878038512&partnerID=8YFLogxK
U2 - 10.1038/srep01087
DO - 10.1038/srep01087
M3 - Article
C2 - 23336069
AN - SCOPUS:84878038512
SN - 2045-2322
VL - 3
JO - Scientific reports
JF - Scientific reports
M1 - 1087
ER -