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© The Rockefeller University Press, 0021-9525/2000//769 $5.00
The Journal of Cell Biology, Volume 148, Number 4, , 2000 769-778

A Transmembrane Segment Determines the Steady-State Localization of an Ion-Transporting Adenosine Triphosphatase

^a Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510
^b Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510
Department of Cellular and Molecular Biology, 333 Cedar St., Sterling Hall of Medicine, BE-30, New Haven, CT 06510.(203) 785-4951(203) 785-6833

ldunbar{at}biomed.med.yale.edu

The H,K-adenosine triphosphatase (ATPase) of gastric parietal cells is targeted to a regulated membrane compartment that fuses with the apical plasma membrane in response to secretagogue stimulation. Previous work has demonstrated that the subunit of the H,K-ATPase encodes localization information responsible for this pump's apical distribution, whereas the β subunit carries the signal responsible for the cessation of acid secretion through the retrieval of the pump from the surface to the regulated intracellular compartment. By analyzing the sorting behaviors of a number of chimeric pumps composed of complementary portions of the H,K-ATPase subunit and the highly homologous Na,K-ATPase subunit, we have identified a portion of the gastric H,K-ATPase, which is sufficient to redirect the normally basolateral Na,K-ATPase to the apical surface in transfected epithelial cells. This motif resides within the fourth of the H,K-ATPase subunit's ten predicted transmembrane domains. Although interactions with glycosphingolipid-rich membrane domains have been proposed to play an important role in the targeting of several apical membrane proteins, the apically located chimeras are not found in detergent-insoluble complexes, which are typically enriched in glycosphingolipids. Furthermore, a chimera incorporating the Na,K-ATPase subunit fourth transmembrane domain is apically targeted when both of its flanking sequences derive from H,K-ATPase sequence. These results provide the identification of a defined apical localization signal in a polytopic membrane transport protein, and suggest that this signal functions through conformational interactions between the fourth transmembrane spanning segment and its surrounding sequence domains.

Key Words: sorting • polarity • epithelia • Na,K- • ATPase • H,K-ATPase

© 2000 The Rockefeller University Press

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