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Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand.

Publication ,  Journal Article
Hein, L; Meinel, L; Pratt, RE; Dzau, VJ; Kobilka, BK
Published in: Mol Endocrinol
August 1997

Angiotensin II (Ang II) binds to two different receptor subtypes, AT1 and AT2 receptors. In many cases, receptor stimulation by Ang II is followed by a rapid desensitization of the intracellular signal transduction and a decrease in cell surface receptor number. The present study was designed to examine by immunofluorescence microscopy the cellular trafficking pathways of Ang II and its AT1a and AT2 receptors in human embryonal kidney 293 cells stably expressing these receptor subtypes. Fluorescently labeled Ang II and AT1a receptors were rapidly internalized into endosomes. AT2 receptors were localized in the plasma membrane and did not undergo endocytosis upon agonist stimulation. After removal of agonist, AT1a receptors recycled to the plasma membrane, whereas fluorescently labeled Ang II was targeted to the lysosomal pathway. Even though no further loss of surface receptor was measurable by ligand binding at steady state, fluorescein-Ang II was continuously internalized, and cycling of receptor between endosomal vesicles and the plasma membrane was detected by antibody feeding. These experiments provide evidence for subtype-specific receptor sorting and internalization of Ang II and its AT1a receptor as a receptor-ligand complex, and they suggest that the sequestration of receptors into endosomes is in dynamic equilibrium with receptor cycling to the plasma membrane. Finally, internalization of AT1a receptors and Ang II persists after desensitization mechanisms have attenuated Ca2+ and inositol 1,4,5-trisphosphate signaling.

Duke Scholars

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

August 1997

Volume

11

Issue

9

Start / End Page

1266 / 1277

Location

United States

Related Subject Headings

  • Receptors, Angiotensin
  • Receptor, Angiotensin, Type 2
  • Receptor, Angiotensin, Type 1
  • Mice
  • Lysosomes
  • Inositol 1,4,5-Trisphosphate
  • Humans
  • Fluorescent Antibody Technique, Direct
  • Fluoresceins
  • Fluorescein
 

Citation

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MLA
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Hein, L., Meinel, L., Pratt, R. E., Dzau, V. J., & Kobilka, B. K. (1997). Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand. Mol Endocrinol, 11(9), 1266–1277. https://doi.org/10.1210/mend.11.9.9975
Hein, L., L. Meinel, R. E. Pratt, V. J. Dzau, and B. K. Kobilka. “Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand.Mol Endocrinol 11, no. 9 (August 1997): 1266–77. https://doi.org/10.1210/mend.11.9.9975.
Hein L, Meinel L, Pratt RE, Dzau VJ, Kobilka BK. Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand. Mol Endocrinol. 1997 Aug;11(9):1266–77.
Hein, L., et al. “Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand.Mol Endocrinol, vol. 11, no. 9, Aug. 1997, pp. 1266–77. Pubmed, doi:10.1210/mend.11.9.9975.
Hein L, Meinel L, Pratt RE, Dzau VJ, Kobilka BK. Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand. Mol Endocrinol. 1997 Aug;11(9):1266–1277.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

August 1997

Volume

11

Issue

9

Start / End Page

1266 / 1277

Location

United States

Related Subject Headings

  • Receptors, Angiotensin
  • Receptor, Angiotensin, Type 2
  • Receptor, Angiotensin, Type 1
  • Mice
  • Lysosomes
  • Inositol 1,4,5-Trisphosphate
  • Humans
  • Fluorescent Antibody Technique, Direct
  • Fluoresceins
  • Fluorescein