IntroductionPolarity is a ubiquitous feature of the biology of eukaryotic cells and entails the establishment and maintenance of spatial and functional asymmetry, triggered by cues from the external and intracellular environments. For example, cell movement in response to chemoattractants causes asymmetric shape changes, generating a leading edge that protrudes at the front of the cell and a rear edge that retracts (Lauffenburger and Horwitz, 1996). Instrumental in this is the establishment of membrane polarity. Molecules such as (glyco)sphingolipids segregate to the two opposing membrane surfaces (GomezMouton et al., 2001) and, by virtue of their ability to organize microdomains, may establish a platform for recruitment of the different molecular machineries required at these locations. Polarity is also apparent in neuronal cells, in which membrane domains are segregated by a diffusion barrier formed by a row of protein 'pickets' assembled on a membrane-cytoskeletal meshwork at the axonal initial segment (Nakada et al., 2003). However, most attention has focused on epithelial cells and it is these that perhaps best exemplify the principles of cell polarity, displaying asymmetric cellular morphology, molecular composition and functional properties.Epithelial cells line many tissues and simultaneously face different environments: the lumen on one side, and adjacent cells and underlying connective tissue on the other. Accordingly, compartmentalization of the cell surface and hence the operation of distinctly localized sorting and retention mechanisms are crucial for their function. Signals triggered by extracellular matrix and cell-cell cues, and relayed by key players such as integrins and E-cadherin-catenin complexes, respectively, cause the establishment of specific intercellular junctions, rearrange the cytoskeletal architecture, and activate sorting mechanisms to generate the so-called apical and basolateral plasma membrane domains (Knust, 2002;Mostov et al., 2003;Nelson, 2003). Tight junctions separate these membrane domains, preventing mixing of membrane proteins and (outer leaflet) lipids between them. Complex signaling and sorting machineries regulate transport to and from either domain. In addition, the apical and basolateral domains communicate by transcytosis, the extent of which depends on the cell type. Here, we briefly summarize what is known about these mechanisms and focus on the role of the subapical compartment (SAC), a subcellular trafficking center that is thought to orchestrate these complex trafficking pathways and is required for the generation and maintenance of epithelial membrane polarity.
Endocytosis and polarity: organization and pathwaysPolarization of epithelial Madin-Darby canine kidney (MDCK) cells establishes separate apical and basolateral membrane domains, but also results in a sixfold increase in the surface area of the lateral membrane (Vega-Salas et al., 1987). This demands high levels of membrane biogenesis, which relies on a variety of closely interconnected signaling, bios...