Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
Department of Mechanical Engineering, Graduate School of Engineering, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2021 Dec 20;584:26-31. doi: 10.1016/j.bbrc.2021.10.080. Epub 2021 Nov 2.
Cdc42 is a key factor in directed cell migration and accumulates at the leading edge of migrating cells. However, what kind of proteins control Cdc42 and when is unclear. After mechanical wounding, protein kinase C α (PKCα), a conventional PKC isozyme, begins to accumulate at the edges of cells adjacent to the wounded cells (WCs). In this study, we hypothesized that PKCα may be implicated in directed cell migration at an early stage before Cdc42 controls the migration. We focused on the spatiotemporal distribution of PKCα, Cdc42, and Rac1 before cell migration. After wounding, at the edges of cells adjacent to the WCs, PKCα accumulation, Cdc42 accumulation, Rac1 accumulation, and filopodia formation occurred in that order. The PKCα inhibitor suppressed Cdc42 accumulation at the cell edges. These results suggest that inhibition of PKCα activity inhibits cell migration. In addition, it is not Cdc42 but PKCα that may decide the direction of cell migration.
Cdc42 是定向细胞迁移的关键因素，它在迁移细胞的前沿聚集。然而，控制 Cdc42 的是哪种蛋白质以及何时控制还不清楚。在机械损伤后，蛋白激酶 Cα（PKCα），一种常规的 PKC 同工酶，开始在靠近受伤细胞（WC）的细胞边缘积累。在这项研究中，我们假设 PKCα 可能在 Cdc42 控制迁移之前的早期阶段参与定向细胞迁移。我们专注于细胞迁移前 PKCα、Cdc42 和 Rac1 的时空分布。在受伤后，在靠近 WC 的细胞边缘，PKCα 积累、Cdc42 积累、Rac1 积累和丝状伪足形成依次发生。PKCα 抑制剂抑制了细胞边缘的 Cdc42 积累。这些结果表明抑制 PKCα 活性抑制了细胞迁移。此外，可能决定细胞迁移方向的不是 Cdc42 而是 PKCα。
