MOLECULAR SORTING IN POLARIZED AND NON-POLARIZED CELLS - COMMON PROBLEMS, COMMON SOLUTIONS

We have been interested in determining how epithelial cells generate a nd maintain their characteristically polarized distributions of membra ne proteins. Our efforts to date strongly indicate that the polarized transport in MDCK cells may be due to a set of discrete targeting dete rminants often found on a membrane protein's cytoplasmic domain. Surpr isingly, these determinants are widely distributed and are not specifi c to proteins expressed in polarized cells. They also appear to functi on in controlling polarized transport along both the biosynthetic and the endocytic (or transcytotic) pathways. Signals for basolateral tran sport have been characterized and, like the cytoplasmic domain signal used by plasma membrane receptors for accumulation at clathrin-coated pits, they often involve a critical tyrosine residue. Although the bas olateral and coated pit signals may also be co-linear, they are not id entical. The basolateral and apical transport determinants are also hi erarchically arranged. Although a single protein may contain one or mo re signals specifying basolateral transport, inactivation of these sig nals appears to reveal a determinant that directs efficient apical tra nsport. Given that the sequence determinants responsible for polarized transport are not restricted to epithelial cells and are related to d eterminants commonly utilized in all cells, it is possible that non-po larized cells contain cognate apical and basolateral pathways that are responsible for 'constitutive' transport from the Golgi to the plasma membrane. The presence of two cognate pathways might confer a high de gree of plasticity to pre-differentiated cells, allowing them rapidly to begin assuming a polarized phenotype in response to extracellular s timuli without requiring the synthesis of epithelial cell-specific tra nsport machinery.