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Related Experiment Videos

An ion-transporting ATPase encodes multiple apical localization signals

C J Gottardi1, M J Caplan

  • 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.

The Journal of Cell Biology
|April 1, 1993
PubMed
Summary

The H,K-ATPase and Na,K-ATPase ion pumps have distinct cellular locations. Both H,K-ATPase subunits independently direct apical localization, while the beta-subunit also influences endocytosis.

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Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Epithelial cells exhibit polarized plasma membranes with distinct protein populations.
  • The Na,K-ATPase is typically basolateral, while H,K-ATPase is apical in gastric parietal cells.

Purpose of the Study:

  • To investigate the molecular signals governing the differential localization of H,K-ATPase and Na,K-ATPase.
  • To determine if subunits of H,K-ATPase contain intrinsic sorting signals.

Main Methods:

  • Expression of full-length and chimeric H,K-ATPase/Na,K-ATPase cDNAs in polarized LLC-PK1 epithelial cells.
  • Analysis of subcellular localization of expressed ion pumps.

Main Results:

  • Both alpha and beta subunits of H,K-ATPase contain independent signals for apical membrane targeting.

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  • The H,K-ATPase beta-subunit has a sequence that mediates its involvement in the endocytic pathway.
  • These findings suggest a functional definition of apical and basolateral domains.
  • Conclusions:

    • Apical localization signals are present on both H,K-ATPase subunits.
    • Epithelial sorting and endocytosis are interconnected processes.
    • Apical and basolateral domains may be functionally defined rather than purely topographic.