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Megalin binds and internalizes angiotensin II.

Publication ,  Journal Article
Gonzalez-Villalobos, R; Klassen, RB; Allen, PL; Navar, LG; Hammond, TG
Published in: Am J Physiol Renal Physiol
February 2005

Megalin is an abundant membrane protein heavily involved in receptor-mediated endocytosis. The major functions of megalin in vivo remain incompletely defined as megalin typically faces specialized milieus such as glomerular filtrate, airways, epididymal fluid, thyroid colloid, and yolk sac fluid, which lack many of its known ligands. In the course of studies on ANG II internalization, we were surprised when only part of the uptake of labeled ANG II into immortalized yolk sac cells (BN-16 cells) was blocked by specific peptide inhibitors and direct competitors of the angiotensin type 1 receptor. This led us to test if megalin was a receptor for ANG II. Four lines of direct evidence demonstrate that megalin and, to a lesser extent, its chaperone protein cubilin are receptors for ANG II. First, in BN-16 cells anti-megalin and anti-cubilin antisera interfere with ANG II uptake. Second, also in BN-16 cells, pure ANG II competes for uptake of a known megalin ligand. Third, in proximal tubule cell brush-border membrane vesicles extracted from mice, anti-megalin antisera interfere with ANG II binding. Fourth, purified megalin binds ANG II directly in surface plasmon resonance experiments. The finding that megalin is a receptor for ANG II suggests a major new function for the megalin pathway in vivo. These results also indicate that ANG II internalization in some tissues is megalin dependent and that megalin may play a role in regulating proximal tubule ANG II levels.

Duke Scholars

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

February 2005

Volume

288

Issue

2

Start / End Page

F420 / F427

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Urology & Nephrology
  • Receptor, Angiotensin, Type 1
  • Polymerase Chain Reaction
  • Mice
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Kidney Tubules, Proximal
  • Animals
  • Angiotensin II
  • 3208 Medical physiology
 

Citation

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MLA
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Gonzalez-Villalobos, R., Klassen, R. B., Allen, P. L., Navar, L. G., & Hammond, T. G. (2005). Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol, 288(2), F420–F427. https://doi.org/10.1152/ajprenal.00243.2004
Gonzalez-Villalobos, Romer, R Bryan Klassen, Patricia L. Allen, L. G. Navar, and Timothy G. Hammond. “Megalin binds and internalizes angiotensin II.Am J Physiol Renal Physiol 288, no. 2 (February 2005): F420–27. https://doi.org/10.1152/ajprenal.00243.2004.
Gonzalez-Villalobos R, Klassen RB, Allen PL, Navar LG, Hammond TG. Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol. 2005 Feb;288(2):F420–7.
Gonzalez-Villalobos, Romer, et al. “Megalin binds and internalizes angiotensin II.Am J Physiol Renal Physiol, vol. 288, no. 2, Feb. 2005, pp. F420–27. Pubmed, doi:10.1152/ajprenal.00243.2004.
Gonzalez-Villalobos R, Klassen RB, Allen PL, Navar LG, Hammond TG. Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol. 2005 Feb;288(2):F420–F427.

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

February 2005

Volume

288

Issue

2

Start / End Page

F420 / F427

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Urology & Nephrology
  • Receptor, Angiotensin, Type 1
  • Polymerase Chain Reaction
  • Mice
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Kidney Tubules, Proximal
  • Animals
  • Angiotensin II
  • 3208 Medical physiology