Establishment and maintenance of cell polarity during leukocyte chemotaxis

Abstract

The term polarity refers to the differential distribution of the macromolecular elements of a cell, resulting in its asymmetry in function, shape and/or content. Polarity is a fundamental property of all metazoan cells in at least some stages, and is pivotal to processes such as epithelial differentiation (apical/basal polarity), coordinated cell activity within the plane of a tissue (planar cell polarity), asymmetric cell division, and cell migration. In the last case, an apparently symmetric cell responds to directional cues provided by chemoattractants, creating a polarity axis that runs from the cell anterior, or leading edge, in which actin polymerization takes place, to the cell posterior (termed uropod in leukocytes), in which acto-myosin contraction occurs. Here we will review some of the molecular mechanisms through which chemoattractants break cell symmetry to trigger directed migration, focusing on cells of the immune system. We briefly highlight some common or apparently contradictory pathways reported as important for polarity in other cells, as this suggests conserved or cell type-specific mechanisms in eukaryotic cell chemotaxis.

Figure 1

Segregation of lipid rafts in leukocytes and mesenchymal-like cells. The scheme depicts leading edge and posterior markers whose association to lipid rafts has been described. Some uropod markers in leukocytes, such as ERM proteins and the adhesion receptors β1 integrin and CD44, localize at the cell front in mesenchymal cells. This probably reflects the different migratory strategies used by each cell type.

Figure 2

Polarity systems in motile cells. Polarity can be described from the perspective of the antagonistic activity of the PI3K/PTEN system, as described for Dictyostelium orientation, the Rac/RhoA system, as described in neutrophils, the Par/Scribble system, as described in T cells, and the segregation of L- and U-rafts, as described in T cells and neutrophils. The interrelationships between these four systems are not well defined. See the text for details.