期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 320, 期 6, 页码 C1153-C1163出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00225.2020
关键词
cofilin; cyclic stretch; nonmuscle myosin II; stress fibers
资金
- KAKENHI [20001007, 25750154, 16H05907, 18H03518]
- Grants-in-Aid for Scientific Research [25750154, 16H05907] Funding Source: KAKEN
Cells adapt to cyclic stretch by selectively disassembling actin stress fibers in the stretch direction, primarily through the mechanosensitive behavior of myosin II. Fast cell shortening can enhance the disassembly of actomyosin bundle stress fibers, with myosin regulatory light-chain mutants affecting the rate of disassembly. Additionally, the presence of an active LIM-kinase-1 mutant can induce similar disassembly of stress fibers by deactivating cofilin, suggesting a previously proposed mechanism may be dispensable.
Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here, we suggest that the mechanosensitive behavior of myosin II, a major crosslinker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light-chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.
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