Integrin-dependent phagocytosis – spreading from microadhesion to new concepts

Abstract

By linking actin dynamics to extracellular components, integrins are involved in a wide range of cellular processes that are associated with or require cytoskeletal remodelling and cellshape changes. One such function is integrin-dependent phagocytosis, a process that several integrins are capable of mediating and that allows the binding and clearance of particles. Integrin-dependent phagocytosis is involved in a wide range of physiological processes, from the clearance of microorganisms and apoptotic-cell removal to extracellular-matrix remodelling. Integrin signalling is also exploited by microbial pathogens for entry into host cells. Far from being a particular property of specific integrins and specialised cells, integrin-dependent uptake is emerging as a general, intrinsic ability of most integrins that is associated with their capacity to signal to the actin cytoskeleton. Integrin-mediated phagocytosis can therefore be used as a robust model in which to study integrin regulation and signalling. Journal of Cell Science 1774 distinct receptors can be devoted to particle recognition ('tethering' receptors) and stimulation of particle uptake ('tickling' receptors) (Zullig and Hengartner, 2004). Interestingly, zipper-like phagocytosis can also take place in non-professional phagocytes, either naturally or following transfection of phagocytic receptors (Caron and Hall, 1998;Underhill and Ozinsky, 2002).Similar to cell adhesion and migration, phagocytosis crucially depends on remodelling of the actin cytoskeleton and on membrane dynamics (DeMali and Burridge, 2003;Niedergang and Chavrier, 2004). Moreover, the signalling pathways that underlie these processes have several regulatory proteins in common, including Rho-family proteins Ridley et al., 2003). Interestingly, distinct Rho GTPases regulate actin polymerisation during phagocytosis and actually define several modes of phagocytosis that are phenotypically different. Indeed, during FcγR-dependent (also referred as type I) uptake, activation of Rac1 and Cdc42 is thought to drive the formation of local pseudopods and membrane ruffles that engulf the particles. By contrast, actin polymerisation during integrin-αMβ2-dependent (referred as type II) phagocytosis is regulated by RhoA activity, and particles that are bound to αMβ2 sink into cells without generating major protrusions (see below and Fig. 2) (Allen and Aderem, 1996; Caron and Hall, 1998).On the basis of the criteria defined above for phagocytosis (particle size, zipper-like receptor tickling, and actin-dependent and Rho-GTPase-dependent uptake), we review here the role of integrins in phagocytosis, both in professional phagocytes and also in cells that are not classically considered phagocytic. We highlight the similarities between the signalling basis of integrin function during adhesion and phagocytic uptake. Not only is phagocytosis the predominant function of certain integrins, it should be seen as an intrinsic ability of most integrins. By extension, integrin-mediated phagocytosis can be proposed a...

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