Department of Molecular and Cellular Physiology, Albany Medical College, 47 New Scotland Avenue, MC-8, Albany, NY, 12208, USA.
Sci Rep. 2020 Jun 30;10(1):10667. doi: 10.1038/s41598-020-67781-1.
Smooth muscle cell migration is essential for many diverse biological processes such as pulmonary/cardiovascular development and homeostasis. Abi1 (Abelson interactor 1) is an adapter protein that has been implicated in nonmuscle cell migration. However, the role and mechanism of Abi1 in smooth muscle migration are largely unknown. Here, Abi1 knockdown by shRNA reduced human airway smooth muscle cell migration, which was restored by Abi1 rescue. Abi1 localized at the tip of lamellipodia and its protrusion coordinated with F-actin at the leading cell edge of live cells. In addition, we identified profilin-1 (Pfn-1), a G-actin transporter, as a new partner for Abi1. Abi1 knockdown reduced the recruitment of Pfn-1 to the leading cell edge. Moreover, Abi1 knockdown reduced the localization of the actin-regulatory proteins c-Abl (Abelson tyrosine kinase) and N-WASP (neuronal Wiskott-Aldrich Syndrome Protein) at the cell edge without affecting other migration-related proteins including pVASP (phosphorylated vasodilator stimulated phosphoprotein), cortactin and vinculin. Furthermore, we found that c-Abl and integrin β1 regulated the positioning of Abi1 at the leading edge. Taken together, the results suggest that Abi1 regulates cell migration by affecting Pfn-1 and N-WASP, but not pVASP, cortactin and focal adhesions. Integrin β1 and c-Abl are important for the recruitment of Abi1 to the leading edge.
平滑肌细胞迁移对于许多不同的生物学过程都是必不可少的，如肺/心血管发育和稳态。Abi1（Abelson 相互作用蛋白 1）是一种衔接蛋白，已被牵连到非肌肉细胞迁移中。然而，Abi1 在平滑肌迁移中的作用和机制在很大程度上仍是未知的。在这里，通过 shRNA 敲低 Abi1 减少了人呼吸道平滑肌细胞的迁移，而通过 Abi1 挽救则恢复了迁移。Abi1 定位于片状伪足的尖端，其突起与活细胞前缘的 F-肌动蛋白协调。此外，我们鉴定出了 Profilin-1（Pfn-1），一种 G 肌动蛋白转运蛋白，是 Abi1 的一个新伴侣。Abi1 敲低减少了 Pfn-1 募集到前缘。此外，Abi1 敲低减少了细胞边缘处肌动蛋白调节蛋白 c-Abl（Abelson 酪氨酸激酶）和 N-WASP（神经元 Wiskott-Aldrich 综合征蛋白）的定位，而不影响其他迁移相关蛋白，包括 pVASP（磷酸化血管扩张刺激磷蛋白）、cortactin 和 vinculin。此外，我们发现 c-Abl 和整合素β1 调节 Abi1 在前沿的定位。综上所述，结果表明 Abi1 通过影响 Pfn-1 和 N-WASP 而不是 pVASP、cortactin 和粘着斑来调节细胞迁移。整合素β1 和 c-Abl 对于 Abi1 募集到前缘是重要的。
