title: The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction.
abstract: 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/cm(2), 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.
authors: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Allison B
authors: AB
authors: Chambliss
authors: Shyam B
authors: SB
authors: Khatau
authors: Nicholas
authors: N
authors: Erdenberger
authors: D Kyle
authors: DK
authors: Robinson
authors: Didier
authors: D
authors: Hodzic
authors: Gregory D
authors: GD
authors: Longmore
authors: Denis
authors: D
authors: Wirtz
mesh_terms: D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D022502:Stress Fibers / Q000378:metabolism; D013314:Stress, Mechanical; D016608:Talin / Q000378:metabolism; D013997:Time Factors; D060589:Zyxin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D034904:Lamin Type A; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485903:Syne2 protein, mouse; D016608:Talin; D060589:Zyxin; C440308:lamin C; C507800:nesprin-3 protein, mouse; D000205:Actomyosin