Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers
Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers
复制标题
DOI：
10.1152/ajpcell.00225.2020
复制
发表时间：
2021-06-01
影响因子：
5.5
通讯作者：
Deguchi，Shinji
中科院分区：
文献类型：
--
作者：
Huang，Wenjing;Matsui，Tsubasa S.;Deguchi，Shinji
细胞适应所施加的周期性拉伸（CS）以规避促炎信号传导的慢性激活。目前，肌动蛋白应力纤维（SF）在拉伸方向上的选择性解体的分子机制，发生在细胞响应CS的早期阶段，仍然存在争议。在这里，我们建议，肌球蛋白II，SF的主要交联剂的机械敏感行为，主要有助于定向拆卸的肌动球蛋白复合物SF在牛血管平滑肌细胞和人U2 OS骨肉瘤细胞。首先，我们确定CS的缩短阶段，超过了速度的固有收缩率的个别SF导致拆卸。为了了解生物学基础，我们研究了表达肌球蛋白调节轻链突变体的效果，发现具有较少肌动球蛋白活性的SF在CS后更迅速地分解。因此，我们创建了一个最小的数学模型，概括了SFs的方向选择性和阈值触发的拆卸的显着特征，以显示拆卸，或者更具体地说，肌动球蛋白束SFs的解束与足够快的细胞缩短增强。我们进一步证明，类似的拆卸的SFs是诱导的存在下，一个活跃的LIM-激酶-1突变体，失活cofilin，这表明cofilin是cofilin，而不是以前提出的机制。
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 cross-linker 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.