Megalin binds and internalizes angiotensin-(1-7).

Published

Journal Article

Megalin is a multiligand receptor heavily involved in protein endocytosis. We recently demonstrated that megalin binds and mediates internalization of ANG II. Although there is a strong structural resemblance between ANG II and ANG-(1-7), their physiological actions and their affinity for the angiotensin type 1 receptor (AT(1)R) are dissimilar. Therefore, the hypothesis of the present work was to test whether megalin binds and internalizes ANG-(1-7). The uptake of ANG-(1-7) was determined by exposure of confluent monolayers of BN/MSV cells (a model representative of the yolk sac epithelium) to fluorescently labeled ANG-(1-7) (100 nM) and measurement of the amount of cell-associated fluorescence after 4 h by flow cytometry. Anti-megalin antisera and an AT(1)R blocker (olmesartan) were used to interfere with uptake via megalin and the AT(1)R, respectively. ANG-(1-7) uptake was prevented by anti-megalin antisera (63%) to a higher degree than olmesartan (13%) (P < 0.001). In analysis by flow cytometry of binding experiments performed in brush-border membrane vesicles isolated from kidneys of CD-1 mice, anti-megalin antisera interfered with ANG-(1-7) binding more strongly than olmesartan (P < 0.05 against positive control). Interactions of megalin with ANG-(1-7) at a molecular level were studied by surface plasmon resonance, demonstrating that ANG-(1-7) binds megalin dose and time dependently and with an affinity similar to ANG II. These results show that the scavenger receptor megalin binds and internalizes ANG-(1-7).

Full Text

Duke Authors

Cited Authors

  • Gonzalez-Villalobos, R; Klassen, RB; Allen, PL; Johanson, K; Baker, CB; Kobori, H; Navar, LG; Hammond, TG

Published Date

  • May 2006

Published In

Volume / Issue

  • 290 / 5

Start / End Page

  • F1270 - F1275

PubMed ID

  • 16380466

Pubmed Central ID

  • 16380466

International Standard Serial Number (ISSN)

  • 1931-857X

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00164.2005

Language

  • eng

Conference Location

  • United States