Force-Induced Calpain Cleavage of Talin Is Critical for Growth, Adhesion Development, and Rigidity Sensing.

Force-Induced Calpain Cleavage of Talin Is Critical for Growth, Adhesion Development, and Rigidity Sensing.
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DOI:
10.1021/acs.nanolett.7b02476
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发表时间:
2017-12-13
期刊:
影响因子:
10.8
通讯作者:
Sheetz MP
Sheetz MP
中科院分区:
材料科学1区
文献类型:
--
作者:
Saxena M;Changede R;Hone J;Wolfenson H;Sheetz MP

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细胞生长取决于细胞-基质粘附的形成,但仍然缺乏详细说明粘附信号传输以控制增殖的机制。在这里,我们发现支架蛋白踝蛋白在早期粘附中经历力诱导裂解,产生细胞周期进展所需的踝蛋白杆片段。不可裂解的踝蛋白的表达会阻碍细胞生长、粘附成熟、适当的机械传感以及 EGF 运动激活的相关特性。此外,在不可切割的全长踝蛋白存在下,踝蛋白杆的表达可挽救细胞生长和其他功能。踝蛋白的裂解存在于早期粘连中,其中还存在取决于钙蛋白酶和 TRPM4 活性以及踝蛋白上力的产生的踝蛋白的快速周转。因此,我们认为talin的一个重要功能是通过早期粘附的裂解来控制细胞周期进程。
Cell growth depends upon formation of cell-matrix adhesions, but mechanisms detailing the transmission of signals from adhesions to control proliferation are still lacking. Here, we find that the scaffold protein talin undergoes force-induced cleavage in early adhesions to produce the talin rod fragment that is needed for cell cycle progression. Expression of noncleavable talin blocks cell growth, adhesion maturation, proper mechanosensing, and the related property of EGF activation of motility. Further, the expression of talin rod in the presence of noncleavable full-length talin rescues cell growth and other functions. The cleavage of talin is found in early adhesions where there is also rapid turnover of talin that depends upon calpain and TRPM4 activity as well as the generation of force on talin. Thus, we suggest that an important function of talin is its control over cell cycle progression through its cleavage in early adhesions.
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