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Related Experiment Videos

Megalin binds and internalizes angiotensin II.

Romer Gonzalez-Villalobos1, R Bryan Klassen, Patricia L Allen

  • 1Tulane Hypertension and Renal Center of Excellence and Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

American Journal of Physiology. Renal Physiology
|October 7, 2004
PubMed
Summary
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Megalin and cubilin are identified as receptors for angiotensin II (ANG II). This discovery reveals a new role for the megalin pathway in regulating ANG II uptake and levels in proximal tubules.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Megalin is a membrane protein involved in endocytosis, but its in vivo functions are not fully understood.
  • Megalin is found in specialized environments lacking many known ligands, complicating functional studies.

Purpose of the Study:

  • To investigate the role of megalin in the internalization of angiotensin II (ANG II).
  • To determine if megalin functions as a receptor for ANG II.

Main Methods:

  • Utilized immortalized yolk sac cells (BN-16) to study ANG II uptake.
  • Employed antisera against megalin and cubilin to assess their role in ANG II uptake.
  • Performed competition assays with ANG II and a known megalin ligand.
  • Analyzed ANG II binding to brush-border membrane vesicles from mouse proximal tubules.

Related Experiment Videos

  • Conducted surface plasmon resonance experiments with purified megalin and ANG II.

    • Main Results:

    • Anti-megalin and anti-cubilin antibodies inhibited ANG II uptake in BN-16 cells.
    • ANG II competed with a known megalin ligand for uptake in BN-16 cells.
    • Anti-megalin antibodies reduced ANG II binding to mouse proximal tubule membrane vesicles.
    • Purified megalin directly bound ANG II in vitro.

    Conclusions:

    • Megalin and cubilin act as receptors for ANG II.
    • This finding establishes a novel function for the megalin pathway.
    • Megalin-dependent ANG II internalization occurs in certain tissues.
    • Megalin may regulate ANG II levels in proximal tubules.