Cited by 103Cellular transport and secretionReceptor Mechanisms and SignalingProtein Kinase Regulation and GTPase Signaling

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Distinct Pathways for the Trafficking of Angiotensin II and Adrenergic Receptors from the Endoplasmic Reticulum to the Cell Surface

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Wu, Guangyu, Zhao, Guiqing, He, Youe·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m305707200

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Abstract

The molecular mechanism underlying the transport of G protein-coupled receptors from the endoplasmic reticulum (ER) to the cell surface is poorly understood. This issue was addressed by determining the role of Rab1, a Ras-related small GTPase that coordinates vesicular protein transport in the early secretory pathway, in the subcellular distribution and function of the angiotensin II type 1A receptor (AT1R), beta2-adrenergic receptor (AR), and alpha2B-AR in HEK293T cells. Inhibition of endogenous Rab1 function by transient expression of dominant-negative Rab1 mutants or Rab1 small interfering RNA (siRNA) induced a marked perinuclear accumulation and a significant reduction in cell-surface expression of AT1R and beta2-AR. The accumulated receptors were colocalized with calregulin (an ER marker) and GM130 (a Golgi marker), consistent with Rab1 function in regulating protein transport from the ER to the Golgi. In contrast, dominant-negative Rab1 mutants and siRNA had no effect on the subcellular distribution of alpha2B-AR. Similarly, expression of dominant-negative Rab1 mutants and siRNA depletion of Rab1 significantly attenuated AT1R-mediated inositol phosphate accumulation and ERK1/2 activation and beta2-AR-mediated ERK1/2 activation, but not alpha2B-AR-stimulated ERK1/2 activation. These data indicate that Rab1 GTPase selectively regulates intracellular trafficking and signaling of G protein-coupled receptors and suggest a novel, as yet undefined pathway for movement of G pro…

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Authors: Wu, G., Zhao, G., & He, Y.
Affiliations: Louisiana State University (US)
Louisiana State University Health Sciences Center New Orleans (US)
Corresponding author: Wu, Guangyu
ORCID: Wu, Guangyu
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-11
Volume: 278
Issue: 47
Pages: 47062-47069
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m305707200
OpenAlex: W2059443787
Cited by: 103
References: 53
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 9 · 2014: 2 · 2013: 4 · 2012: 6
FWCI: 2.31
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6170 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: Rab1, G protein-coupled receptor trafficking, endoplasmic reticulum to Golgi transport, angiotensin II type 1a receptor, beta2-adrenergic receptor, alpha2B-adrenergic receptor, ERK1/2 activation, inositol phosphate accumulation, receptor subcellular distribution, HEK293T cells
MeSH terms: Animals, Cell Line, Cell Membrane, Endoplasmic Reticulum, Golgi Apparatus, Humans, Inositol Phosphates, Receptors, Adrenergic, Transfection, Receptors, Adrenergic, alpha-2, Receptors, Adrenergic, beta-2, rab1 GTP-Binding Proteins, Mitogen-Activated Protein Kinases, Protein Transport, Receptors, G-Protein-Coupled, Receptor, Angiotensin, Type 1, Mitogen-Activated Protein Kinase 3, Rats

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Distinct Pathways for the Trafficking of Angiotensin II and Adrenergic Receptors from the Endoplasmic Reticulum to the Cell Surface

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