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PMID: 22870384 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Actin cap associated focal adhesions and their distinct role in cellular mechanosensing.

Scientific reports ·Vol. 2 ·2012-00-00 ·Pages 555

Kim DH, Khatau SB, Feng Y, Walcott S, Sun SX, Longmore GD, Wirtz D

Abstract

The ability for cells to sense and adapt to different physical microenvironments plays a critical role in development, immune responses, and cancer metastasis. Here we identify a small subset of focal adhesions that terminate fibers in the actin cap, a highly ordered filamentous actin structure that is anchored to the top of the nucleus by the LINC complexes; these differ from conventional focal adhesions in morphology, subcellular organization, movements, turnover dynamics, and response to biochemical stimuli. Actin cap associated focal adhesions (ACAFAs) dominate cell mechanosensing over a wide range of matrix stiffness, an ACAFA-specific function regulated by actomyosin contractility in the actin cap, while conventional focal adhesions are restrictively involved in mechanosensing for extremely soft substrates. These results establish the perinuclear actin cap and associated ACAFAs as major mediators of cellular mechanosensing and a critical element of the physical pathway that transduce mechanical cues all the way to the nucleus.

MeSH Terms
Actin Capping Proteins/metabolism Actinin/metabolism Actins/metabolism Animals Cell Adhesion/physiology Cell Communication/physiology Cell Nucleus/metabolism Fibroblasts/metabolism Focal Adhesion Protein-Tyrosine Kinases/metabolism Focal Adhesions/metabolism Human Umbilical Vein Endothelial Cells/metabolism Humans Mice Myosin Type II/metabolism
Chemicals
Actin Capping Proteins Actins Actinin Focal Adhesion Protein-Tyrosine Kinases Myosin Type II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kim Dong-Hwee
Johns Hopkins Physical Sciences in Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Khatau Shyam B
Feng Yunfeng
Walcott Sam
Sun Sean X
Longmore Gregory D
Wirtz Denis
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Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
Published
2012-00-00
Epub
2012-00-03
Pages
555
Language
English
Region
England
NLM ID
101563288
PMCID
PMC3412326
Subset
IM
Grants
NCI NIH HHS · U54 CA143868 · United States
NCI NIH HHS · T32 CA130840 · United States
NIGMS NIH HHS · R01GM084204 · United States
NCI NIH HHS · U54CA143868 · United States
NIGMS NIH HHS · R01 GM084204 · United States
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