Epithelial cell polarity: new perspectives.

All epithelial cells possess two distinct plasma membrane domains. The apical and basolateral domains differ in protein and lipid composition, and this allows the cell to perform a variety of vectorial functions. Structures involved in generating and maintaining these distinct membrane domains include the tight junction, which serves to restrict lateral diffusion within the membrane, and the cortical cytoskeleton, which can selectively bind and retain transmembrane proteins at a particular surface. A major means to generating membrane asymmetry lies in the ability of the cell to sort apical and basolateral proteins and target them to appropriate destinations. This sorting occurs predominantly at two intracellular sites: the trans-Golgi network, and the basolateral endosome. Constitutive protein traffic in epithelial cells has recently been shown to be regulated via classical signal transduction pathways involving heterotrimeric G proteins and protein kinases. The diversion of apical and basolateral proteins into specific pathways can be mediated by signals contained within these proteins. Apical sorting information is thought to be localized in the luminal domain of transmembrane proteins, and in the case of proteins anchored to the membrane via a GPI anchor, apical sorting information is provided by the lipid moiety. In contrast, basolateral signals have been identified in the cytoplasmic domain of transmembrane proteins. Shared similarities between basolateral signals and those required for endocytosis have suggested that these two sorting processes are mechanistically related.

A novel pathway for secretory proteins?

In eukaryotes, most proteins which are transported to the extracellular space, into mitochondria or into chloroplasts are synthesized as precursor polypeptides containing cleavable N-terminal signal or targeting sequences. We have searched the literature for proteins that are exported from the cytosol without being proteolytically processed. Some of these proteins contain uncleaved signal or targeting sequences. However, among secretory proteins there is a class that does not possess hydrophobic signal sequences and appears to leave the cell by a secretory pathway clearly distinct from the classical route through the endoplasmic reticulum and Golgi apparatus.