Leukocyte uropod formation and membrane/cytoskeleton linkage in immune interactions

Abstract: The acquisition of a cell polarity is a crucial requirement for migration, activation, and apoptosis of leukocytes. The polarization of leuko-cytes involves the formation of two distinct poles: the leading edge—the attachment cell site to the substrate allowing directional movements of the cell—and on the opposite side, the uropod—mostly involved in cell-to-cell interaction and in a variety of leukocyte activities including activation and apo-ptosis. However, the uropod takes shape in neutro-phils, monocytes, and natural killer cells, and the formation of this cell protrusion seems to exert an important role in immune interactions. In fact, the polarization sites of leukocytes are involved in a complex cross-talk between cells and extracellular matrix components, and a number of receptors and counter-receptors crowd in the contact sites to allow efficient cell-to-cell or cell–substrate interac-tion. The membrane/cytoskeleton interaction plays a crucial role in tuning these activities and in “pre-disposing ” leukocytes to their function through the acquisition of a polarized phenotype. This review is focused on the mechanisms underlying the forma-tion of the leukocyte uropod, the role of cytoskel-eton in defining its structure and function, and the involvement of the uropod in the complex inter-play between immune cells. J. Leukoc. Biol. 73