On the Role of Calpain and Rho Proteins in Regulating Integrin-induced Signaling

Summary

The integrin family of transmembrane receptors plays an essential role in inducing the adhesion of cells to the extracellular matrix. In some cases, members of this family of receptors can bind soluble ligands or can bind receptors on other cells and, in this way, mediate interactions between cells. In all cases, once an integrin has bound, ligand signals are transmitted across the occupied integrin. These signals culminate in changes in the behavior of the cell appropriate for the adherent state of the cell. For example, in the case of platelets, an end result of the signaling induced by binding of fibrinogen to αIIbβ3 in a platelet aggregate is a reorganization of the cytoskeleton that leads to retraction of externally-bound fibrin by clots.^1,2 In the case of neutrophils, cytoskeletal changes following the integrininduced interaction of neutrophils with endothelial cells lead to the migration of neutrophils into a site of injury.^3,4 Other examples of the consequences of integrin-induced signaling in adherent cells include the trafficking of lymphocytes and migration of cells during development, angiogenesis, and metastasis.^5-7

Numerous signaling molecules have been shown to be activated following integrin-ligand interactions.⁸ Many of these associate in complexes with ligand-occupied integrin and cytoskeletal proteins. However, in general, little is known about the key steps involved regarding integrin-induced changes in the behavior of adherent cells. The present chapter reviews steps involved in integrin-induced signaling, describes the evidence that calpain is one of the signaling molecules involved in this signal transduction, and discusses potential mechanisms by which cleavage of cytoskeletal proteins and signaling molecules by calpain may regulate the integrin-induced changes in cell behavior.

• References

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