Substrate stiffness induces nuclear localization of myosin regulatory light chain to suppress apoptosis

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-MRLC via ZIPK. 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.

Automated summary

Stiffness of the extracellular matrix plays a vital role in regulating biological responses, and this study identifies nuclear diphosphorylated myosin regulatory light chain (2P-MRLC) as a critical mediator in suppressing apoptosis in response to substrate stiffness. The kinase ZIPK and actin fiber formation are involved in promoting the nuclear localization of 2P-MRLC in response to stiff substrates. 2P-MRLC, in turn, regulates the expression of MafB and inhibits apoptosis in response to substrate stiffness, revealing a new mechanism in mechanotransduction.