Kuragano Masahiro, Murakami Yota, Takahashi Masayuki
Graduate School of Chemical Science and Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan.
Graduate School of Chemical Science and Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan; Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan.
Biochem Biophys Res Commun. 2018 Mar 25;498(1):25-31. doi: 10.1016/j.bbrc.2018.02.171. Epub 2018 Feb 24.
Nonmuscle myosin II (NMII) plays an essential role in directional cell migration. In this study, we investigated the roles of NMII isoforms (NMIIA and NMIIB) in the migration of human embryonic lung fibroblasts, which exhibit directionally persistent migration in an intrinsic manner. NMIIA-knockdown (KD) cells migrated unsteadily, but their direction of migration was approximately maintained. By contrast, NMIIB-KD cells occasionally reversed their direction of migration. Lamellipodium-like protrusions formed in the posterior region of NMIIB-KD cells prior to reversal of the migration direction. Moreover, NMIIB KD led to elongation of the posterior region in migrating cells, probably due to the lack of load-bearing stress fibers in this area. These results suggest that NMIIA plays a role in steering migration by maintaining stable protrusions in the anterior region, whereas NMIIB plays a role in maintenance of front-rear polarity by preventing aberrant protrusion formation in the posterior region. These distinct functions of NMIIA and NMIIB might promote intrinsic and directed migration of normal human fibroblasts.
非肌肉肌球蛋白II（NMII）在细胞定向迁移中起着至关重要的作用。在本研究中，我们调查了NMII亚型（NMIIA和NMIIB）在人胚肺成纤维细胞迁移中的作用，这些细胞以固有方式表现出定向持续迁移。NMIIA基因敲低（KD）的细胞迁移不稳定，但其迁移方向大致保持。相比之下，NMIIB-KD细胞偶尔会逆转其迁移方向。在迁移方向逆转之前，NMIIB-KD细胞的后部区域形成了片状伪足样突起。此外，NMIIB基因敲除导致迁移细胞后部区域伸长，这可能是由于该区域缺乏承载应力纤维。这些结果表明，NMIIA通过在前部区域维持稳定的突起在引导迁移中发挥作用，而NMIIB通过防止后部区域异常突起形成在维持前后极性中发挥作用。NMIIA和NMIIB的这些不同功能可能促进正常人成纤维细胞的固有和定向迁移。
