The integrin-actin connection, an eternal love affair

Abstract

Integrin receptors connect the extracellular matrix to the actin cytoskeleton. This interaction can be viewed as a cyclical liaison, which develops again and again at new adhesion sites only to cease at sites of de-adhesion. Recent work has demonstrated that multidomain proteins play crucial roles in the integrin-actin connection by providing a high degree of regulation adjusted to the needs of the cell. In this review we present several examples of this paradigm and with special emphasis on the ILK-PINCH-parvin complex, which amply demonstrates how structural and signalling functions are linked together.

Fig. 1. Overview of different pathways by which integrin can link to the actin cytoskeleton. The molecules are not drawn to scale.

Fig. 2. Talin associates with PIPKIγ, which produces PIP2. PIP2 binds to talin, strengthening the interaction between talin and integrin. PIP2 also binds to vinculin, which then interacts with talin. PIP2 on vinculin is replaced by actin filaments. PIP2-associated vinculin can transiently bind to activated Arp2/3 complex, which nucleates actin polymerization. Talin is an antiparallel homodimer. For reasons of simplicity, binding partners of the second talin molecules are not shown. The molecules are not drawn to scale.

Fig. 3. ILK recruits several adaptor proteins that modulate actin dynamics or actin attachment to the integrin adhesion site either directly or indirectly. In addition, ILK can be located to the plasma membrane through interactions with phospholipids. Membrane binding activates the kinase function, subsequent to the phosphorylation of Akt and GSK3. RTK, receptor tyrosine kinase; ILKAP, ILK-associated phosphatase. The molecules are not drawn to scale.