AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

  • Jennifer L. Whiting
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • Leah Ogier
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • Katherine A. Forbush
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • Paula Bucko
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • Janani Gopalan
    Department of Pharmacology, University of Washington, Seattle, WA 98195
  • Ole-Morten Seternes
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • Lorene K. Langeberg
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
  • John D. Scott
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;

書誌事項

公開日
2016-07-11
DOI
  • 10.1073/pnas.1607745113
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:title>Significance</jats:title> <jats:p>Systemic control of water homeostasis is a vital physiological process. Vasopressin-regulated reabsorption of water through aquaporin-2 (AQP2) water pores in the kidney preserves fluid balance and results in more concentrated urine. We have discovered that the scaffolding protein A-Kinase Anchoring Protein 220 (AKAP220) controls vasopressin-independent aspects of AQP2 trafficking at apical membranes of cells of the kidney-collecting ducts. We postulate that this proceeds via a molecular mechanism that evokes RhoA-mediated modulation of “actin barrier” dynamics. Loss of AKAP220 leads to accumulation of AQP2 at the apical plasma membrane and reduces urine-diluting capacity during overhydration. This phenotype may be clinically relevant, as accumulation of AQP2 at the apical membrane is the desired therapeutic outcome when treating patients with certain renal disorders, including nephrogenic diabetes insipidus.</jats:p>

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