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Roles of the G protein-coupled receptor kinase 2 and Rab5 in α1B-adrenergic receptor function and internalization.

Authors
  • Hernández-Espinosa, David A1
  • Reyes-Cruz, Guadalupe2
  • García-Sáinz, J Adolfo3
  • 1 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, Ciudad Universitaria, Ciudad de México, 04510, Mexico. , (Mexico)
  • 2 Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados, CINVESTAV-IPN,Col, Pedro Zacatenco, Ciudad de México, 07360, Mexico. , (Mexico)
  • 3 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, Ciudad Universitaria, Ciudad de México, 04510, Mexico. Electronic address: [email protected] , (Mexico)
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Dec 04, 2019
Volume
867
Pages
172846–172846
Identifiers
DOI: 10.1016/j.ejphar.2019.172846
PMID: 31811856
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cells expressing eGFP-tagged Rab5 (wild-type or the GDP-Rab5 mutant) and the DsRed-tagged α1B-adrenergic receptors were employed and the roles of GRK2 were studied utilizing paroxetine and the dominant-negative mutant of GRK2 (DN-GRK2). The following parameters were studied: a) FRET (as an index of α1B-adrenergic receptor-Rab5 interaction): b) intracellular accumulation of DsRed fluorescence (receptor internalization); c) α1B-adrenergic receptor phosphorylation, and d) noradrenaline-induced increase in intracellular calcium concentration. Noradrenaline increased α1B-adrenergic receptor-Rab5 interaction, which was blocked by paroxetine and by expression of the dominant-negative GRK2 mutant. Similarly, paroxetine and expression of the DN-GRK2 or the GDP-Rab5 mutants markedly decreased receptor internalization, α1B-adrenergic receptor phosphorylation, and attenuated the ability of the adrenergic agonist to induce homologous desensitization (calcium signaling). The S406, 410,412A α1B-adrenergic receptor mutant did not reproduce the actions of GRK2 inhibition. The data indicate that GRK2 and Rab5 play key roles in α1B-adrenergic receptor phosphorylation, internalization, and desensitization. The possibility that Rab5 might form part of a signaling complex is suggested, as well as that GDP-Rab5 might interfere with the ability of GRK2 to catalyze α1B-adrenergic receptor phosphorylation. Copyright © 2019 Elsevier B.V. All rights reserved.

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