Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, NY 12208, USA.
Cells. 2022 Jul 29;11(15):2334. doi: 10.3390/cells11152334.
Airway smooth muscle cell migration plays an essential role in airway development, repair, and remodeling. Smooth muscle myosin II has been traditionally thought to localize in the cytoplasm solely and regulates cell migration by affecting stress fiber formation and focal adhesion assembly. In this study, we unexpectedly found that 20-kDa myosin light chain (MLC) and myosin-11 (MYH11), important components of smooth muscle myosin, were present at the edge of lamellipodia. The knockdown of MLC or MYH11 attenuated the recruitment of c-Abl, cortactinProfilin-1 (Pfn-1), and Abi1 to the cell edge. Moreover, myosin light chain kinase (MLCK) colocalized with integrin β1 at the tip of protrusion. The inhibition of MLCK attenuated the recruitment of c-Abl, cortactin, Pfn-1, and Abi1 to the cell edge. Furthermore, MLCK localization at the leading edge was reduced by integrin β1 knockdown. Taken together, our results demonstrate that smooth muscle myosin localizes at the leading edge and orchestrates the recruitment of actin-regulatory proteins to the tip of lamellipodia. Mechanistically, integrin β1 recruits MLCK to the leading edge, which catalyzes MLC phosphorylation. Activated myosin regulates the recruitment of actin-regulatory proteins to the leading edge, and promotes lamellipodial formation and migration.
气道平滑肌细胞迁移在气道发育、修复和重塑中起着至关重要的作用。传统上认为，平滑肌肌球蛋白 II 仅定位于细胞质中，通过影响应力纤维的形成和黏着斑的组装来调节细胞迁移。在这项研究中，我们出人意料地发现，20kDa 肌球蛋白轻链（MLC）和肌球蛋白-11（MYH11）是平滑肌肌球蛋白的重要组成部分，存在于片状伪足的边缘。MLC 或 MYH11 的敲低削弱了 c-Abl、桩蛋白（cortactin）、 Profilin-1（Pfn-1）和 Abi1 向细胞边缘的募集。此外，肌球蛋白轻链激酶（MLCK）与整合素 β1 在突起的尖端共定位。MLCK 的抑制削弱了 c-Abl、cortactin、Pfn-1 和 Abi1 向细胞边缘的募集。此外，整合素 β1 的敲低降低了 MLCK 在前沿的定位。总之，我们的结果表明，平滑肌肌球蛋白定位于前沿，并协调肌动蛋白调节蛋白募集到片状伪足的尖端。从机制上讲，整合素 β1 将 MLCK 募集到前沿，其催化 MLC 磷酸化。激活的肌球蛋白调节肌动蛋白调节蛋白向前沿的募集，促进片状伪足的形成和迁移。
