Abstract
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.
Highlights
Smooth muscle cell migration is essential for many biological processes such as pulmonary/cardiovascular development and homeostasis
Actin cytoskeletal reorganization is regulated by various actin-regulatory proteins such as cortactin, glia maturation factor-γ (GMFγ), profilin-1 (Pfn-1) and vasodilator-stimulated phosphoprotein (VASP)
We found that wild type (WT) Abi[1], but not Abi1∆PP mutant, localized at the tip of lamellipodia (Fig. 3C)
Summary
Smooth muscle cell migration is essential for many diverse biological processes such as pulmonary/ cardiovascular development and homeostasis. In addition to N-WASP, Abi[1] regulates recruitment of Pfn-1 to the leading cell edge and migration. These results suggest that Abi[1] plays a role in regulating human smooth muscle cell migration. Immunostaining showed that both Pfn-1 and pVASP (Ser-157) (indication of VASP activation)[19] were positioned at the leading cell edge of smooth muscle cells (Fig. 3A).
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