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Filamin A protects cells against force‐induced apoptosis by stabilizing talin‐ and vinculin‐containing cell adhesions
Author(s) -
Pinto Vanessa I.,
Senini Vincent W.,
Wang Yongqiang,
Kazembe Mwayi P.,
McCulloch Christopher A.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-233759
Subject(s) - filamin , flna , vinculin , focal adhesion , microbiology and biotechnology , apoptosis , chemistry , integrin , gene knockdown , programmed cell death , cell adhesion , cell , signal transduction , biology , cytoskeleton , biochemistry
In mechanically loaded tissues such as weight‐bearing joints, myocardium, and periodontal ligament, pathophysiological forces can disrupt cell‐matrix contacts, which can induce cell death, leading to tissue and organ dysfunction. Protection against force‐induced cell death may be mediated by filamin A (FLNa), an actin‐binding protein that regulates β1 integrin‐mediated cell adhesion. We examined the affect of filamin expression on collagen distribution and cell death in the periodontal ligament, a force‐loaded tissue. Conditional deletion of FLNa in fibroblasts was associated with 2‐fold increase of acellular areas in periodontal ligament and 7‐fold higher proportions of apoptotic cells. In cultured fibroblasts with FLNa knockdown, we examined the affect of supraphysiological forces (1 pN/μm 2 cell area; applied through the β1 integrin) on recruitment of talin and vinculin to focal adhesions and on apoptosis. Compared with the wild type, FLNa‐knockdown cells exhibited 3‐fold increases in floating cells after overnight force application and a 2‐fold increase in cell detachment. Force induced time‐dependent reductions ( P <0.05) in the numbers of activated β1 integrin‐, talin‐, and vinculin‐stained adhesions in FLNa‐knockdown compared with those in wild‐type cells. We conclude that FLNa protects against apoptosis in force‐loaded cells, and this protection is mediated by enhanced formation and maturation of matrix adhesions.—Pinto, V. I., Senini, V. W., Wang, Y., Kazembe, M. P., McCulloch, C. A. Filamin A protects cells against force‐induced apoptosis by stabilizing talin and vinculin‐containing cell adhesions. FASEB J . 28, 453–463 (2014). www.fasebj.org