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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
Summary
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.
- 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.