Sorting of ion transport proteins in polarized cells

Abstract

The plasma membranes of polarized epithelial cells and neurons express distinct populations of ion transport proteins in their differentiated plasma membrane domains. In order to understand the mechanisms responsible 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 taken advantage of two closely related families of ion transport proteins whose members are concentrated in different epithelial plasmalemmal domains. The H+,K+-ATPase and the Na+,K+-ATPase are closely related members of the E1-E2 family of ion transporting ATPases. Despite their high degree of structural and functional homology, they are concentrated on different surfaces of polarized epithelial cells and pursue distinct routes to the cell surface in cells which manifest a regulated delivery pathway. We have transfected cDNAs encoding these pumps' subunit polypeptides, as well as chimeras derived from them, in a variety of epithlial and non-epithelial cell types. Our observations suggest that these pumps encode multiple sorting signals whose relative importance and functions may depend upon the cell type in which they are expressed. 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 ion pumps and neurotransmitter re-uptake cotransporters expressed endogenously and by transfection in neurons and epithelial cells, respectively. We find that one of the classes of proteins we studied obeys the correlation 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 different uses in different cell types or under different physiological conditions.