SORTING OF ION-TRANSPORT PROTEINS IN POLARIZED CELLS

The plasma membranes of polarized epithelial cells and neurons express distinct populations of ion transport proteins in their differentiate d plasma membrane domains. In order to understand the mechanisms respo nsible for this polarity it will be necessary to elucidate the nature both of sorting signals and of the cellular machinery which recognizes and acts upon them. In our efforts to study sorting signals we have t aken advantage of two closely related families of ion transport protei ns whose members are concentrated in different epithelial plasmalemmal domains. The H+,K+-ATPase and the Na+,K+-ATPase are closely related m embers of the E(1)-E(2) family of ion transporting ATPases. Despite th eir high degree of structural and functional homology, they are concen trated on different surfaces of polarized epithelial cells and pursue distinct routes to the cell surface in cells which manifest a regulate d delivery pathway. We have transfected cDNAs encoding these pumps' su bunit polypeptides, as well as chimeras derived from them, in a variet y of epithlial and non-epithelial cell types. Our observations suggest that these pumps encode multiple sorting signals whose relative impor tance and functions may depend upon the cell type in which they are ex pressed. Recent evidence suggests that the sorting mechanisms employed by epithelial cells may be similar to those which operate in neurons. We have examined this proposition by studying the distributions of io n pumps and neurotransmitter re-uptake cotransporters expressed endoge nously and by transfection in neurons and epithelial cells, respective ly. We find that one of the classes of proteins we studied obeys the c orrelation between neuronal and epithelial sorting while another does not. Our data are consistent with the possibility that sorting signals and sorting mechanisms are extremely plastic and can be adapted to di fferent uses in different cell types or under different physiological conditions.