A basolateral sorting signal is encoded in the alpha-subunit of Na-K-ATPase

The American Journal of Physiology
T R MuthM J Caplan

Abstract

Na-K-ATPase and H-K-ATPase are highly homologous ion pumps that exhibit distinct plasma membrane distributions in epithelial cells. We have studied the alpha-subunits of these heterodimeric pumps to identify the protein domains responsible for their polarized sorting. A chimeric alpha-subunit construct (N519H) was generated in which the first 519 amino acid residues correspond to the Na-K-ATPase sequence and the remaining 500 amino acids are derived from the H-K-ATPase sequence. In stably transfected LLC-PK1 cell lines, we found that the N519H chimera is restricted to the basolateral surface under steady-state conditions, suggesting that residues within the NH2-terminal 519 amino acids of the Na-K-ATPase alpha-subunit contain a basolateral sorting signal. H-K-ATPase beta-subunit expressed alone in LLC-PK1 cells accumulates at the apical surface. When coexpressed with N519H, the H-K-ATPase beta-subunit assembles with this chimera and accompanies it to the basolateral surface. Thus the NH2-terminal basolateral signal in the Na-K-ATPase alpha-subunit masks or is dominant over any apical sorting information present in the beta-polypeptide. In gastric parietal cells, the H-K-ATPase beta-subunit targets the H-K-ATPase to an intracell...Continue Reading

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Citations

Aug 18, 2006·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Markus LernerJürgen Reinhardt
Aug 15, 2008·American Journal of Physiology. Renal Physiology·Rebecca J Clifford, Jack H Kaplan
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Jul 22, 2009·The Journal of Cell Biology·Glen A FarrMichael J Caplan
May 7, 2010·Molecular Biology of the Cell·Teresita Padilla-BenavidesLiora Shoshani
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Nov 19, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Pedro Gomes, Patrício Soares-da-Silva
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Aug 28, 1998·Current Opinion in Cell Biology·M J Caplan
Jul 28, 2001·Kidney International·M J Caplan
Jun 5, 2003·Biochemical Pharmacology·Naomi MoritaKazuo Nakayama

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