Substrate stiffness induces nuclear localization of myosin regulatory light chain to suppress apoptosis
Substrate stiffness induces nuclear localization of myosin regulatory light chain to suppress apoptosis
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DOI：
10.1002/1873-3468.14592
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发表时间：
2023-02-13
期刊：
影响因子：
3.5
通讯作者：
Haga，Hisashi
中科院分区：
文献类型：
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作者：
Onishi，Katsuya;Ishihara，Seiichiro;Haga，Hisashi
细胞外基质的硬度调节各种生物反应，但反应机制知之甚少。在这里，我们发现，核二磷酸化肌球蛋白调节轻链（2 P-MRLC）是一个关键的机械调节剂，抑制细胞凋亡，对底物的刚度。刚性基质促进2 P-MRLC的核定位。拉链相互作用蛋白激酶[ZIPK;也称为死亡相关蛋白激酶3（DAPK 3）]是MRLC的一种激酶，响应于刚性底物而定位于细胞核中，并促进2 P-MRLC的细胞核定位。此外，由基底刚度诱导的肌动蛋白纤维形成促进了2 P-MRLC通过ZIPK的核定位。2 P-MRLC对底物硬度的响应抑制了MAF bZIP转录因子B（Maf B）的表达并抑制了细胞凋亡。这些发现揭示了一个新确定的MRLC在机械转导的作用。
Stiffness of the extracellular matrix regulates various biological responses, but the response mechanisms are poorly understood. Here, we found that the nuclear diphosphorylated myosin regulatory light chain (2P‐MRLC) is a critical mechanomediator that suppresses apoptosis in response to substrate stiffness. Stiff substrates promoted the nuclear localization of 2P‐MRLC. Zipper‐interacting protein kinase [ZIPK; also known as death‐associated protein kinase 3 (DAPK3)], a kinase for MRLC, was localized in the nucleus in response to stiff substrates and promoted the nuclear localization of 2P‐MRLC. Moreover, actin fiber formation induced by substrate stiffness promoted the nuclear localization of 2P‐MRLCviaZIPK. 2P‐MRLC in response to substrate stiffness suppressed the expression of MAF bZIP transcription factor B (MafB) and repressed apoptosis. These findings reveal a newly identified role of MRLC in mechanotransduction.