Polarization of the motile cell

A polarized cell is one which presents a cellular region or domain which is morphologically or functionally distinct from the rest of the cell. The best-studied examples of polarized cellular domains are the apical and basolateral membranes of epithelial cells and the axon and dendrites of neuronal cells, however, cellular polarization is a functional aspect of almost every cell type. A polarized cellular domain forms via cytoskeletal rearrangement induced by a spatial cue and its distinctive protein composition is generated by retention mechanisms and directed protein targeting (Drubin and Nelson, 1996). In the case of the polarized epithelial cell, activation of cadherins and integrins by extracellular contacts stimulates the assembly of the actin-based cytoskeleton which serves as the scaffold for the formation of the lateral adherens and tight junctions and the basolateral ankyrin-fodrin submembrane cytoskeleton. Directed protein targeting, either from the Golgi apparatus or recycling via the endocytic apparatus, maintains the distinct protein composition of the apical and basolateral membrane domains (Rodriguez-Boulan and Powell, 1992; Keller and Simons, 1997). While the tight junction contributes to the maintenance of epithelial cell polarization by preventing diffusion of proteins between the apical and basolateral plasma membranes, polarized domains are established in other cell types in the absence of the barrier function of the tight junction (Rodriguez-Boulan and Powell, 1992; Drubin and Nelson, 1996; Keller and Simons, 1997). In the case of the motile cell, cytoplasmic extension in the form of pseudopodia leads to the formation of new cellsubstrate contacts in the direction of cellular displacement at the leading edge and the dissociation of cell-substrate contacts at the trailing edge. Cellular contraction causes the displacement of cellular organelles and cytoplasm towards the newly stabilized pseudopod incorporating the pseudopod into the body of the cell. The repeated, directional extension and stabilization of pseudopodia constitutes the basic mechanism by which cells move over a substrate (for review see Lauffenberger and Horwitz, 1996). Pseudopodia are morphologically diverse and include lamellipodia which are flat lamellar extensions and filipodia which are pointed protrusions. These specialized cellular domains are membrane protrusions rich in actin but devoid of cellular organelles and microtubules (Small, 1981; Letourneau, 1983; Bridgman and Dailey, 1989). The best-studied pseudopodial projections of motile cells in culture are flat lamellipodia. Extension of lamellipodia occurs via assembly of actin filaments (Wang, 1985; Okabe and Hirokawa, 1989; Symons and Mitchison, 1991) which then move rearward via a myosin based mechanism (Lin et al., 1996). Retrograde actin flow is responsible for the rearward movement of particles on lamellipodia (Heath and Holifield, 1991) and prevents microtubule penetration into lamellipodia (Waterman-Storer and Salmon, 1997; Suter et al., 1998). The directionality of movement of the motile cell can be considered the basis for its polarization. This concept of front1803 Journal of Cell Science 112, 1803-1811 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS5013