Integrins in cell migration

Abstract

Integrin-based adhesion has served as a model for studying the central role of adhesion in migration. In this article, we outline modes of migration, both integrin-dependent and -independent in vitro and in vivo. We next discuss the roles of adhesion contacts as signaling centers and linkages between the ECM and actin that allows adhesions to serve as traction sites. This includes signaling complexes that regulate migration and the interplay among adhesion, signaling, and pliability of the substratum. Finally, we address mechanisms of adhesion assembly and disassembly and the role of adhesion in cellular polarity.

Figure 1.

Focal adhesions and invadopodia. Schematic showing some major compositional and structural differences between focal adhesions and invadopodia. The linkage from integrin to actin could occur through talin or α-actinin in focal adhesions. A large number of signaling complexes are also implicated in adhesive signaling. In general, they reside in large complexes, which are not shown. (Figure is courtesy of Christa Cortesio.)

Figure 2.

Polarity in migrating cells. The schematic shows the localization and functions that establish front-to-back polarity. In gradient sensing, local PIP3 is produced at the leading edge by polarized distributions of PI3 kinase and PTEN (Kölsch et al. 2008; Swaney et al. 2010). At the cell front, adhesions form and turn over and signal to Rho GTPases; these signals lead to actin polymerization via formins and Arp2/3 as well as assembly of new adhesions. Myosin II and microtubules contribute to polarity, the latter occurring through aPKC/PAR complexes. The rear retracts and adhesions release in response to force and other activities like calpain. (Figure is courtesy of Miguel Vicente-Manzanares.)