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The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor.

作者信息

Takahashi Toshimasa, Huang Yibin, Yamamoto Koichi, Hamano Go, Kakino Akemi, Kang Fei, Imaizumi Yuki, Takeshita Hikari, Nozato Yoichi, Nozato Satoko, Yokoyama Serina, Nagasawa Motonori, Kawai Tatsuo, Takeda Masao, Fujimoto Taku, Hongyo Kazuhiro, Nakagami Futoshi, Akasaka Hiroshi, Takami Yoichi, Takeya Yasushi, Sugimoto Ken, Gaisano Herbert Y, Sawamura Tatsuya, Rakugi Hiromi

机构信息

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Department of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada.

出版信息

iScience. 2021 Jan 21;24(2):102076. doi: 10.1016/j.isci.2021.102076. eCollection 2021 Feb 19.

DOI:10.1016/j.isci.2021.102076
PMID:33659870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7890409/
Abstract

Arrestin-dependent activation of a G-protein-coupled receptor (GPCR) triggers endocytotic internalization of the receptor complex. We analyzed the interaction between the pattern recognition receptor (PRR) lectin-like oxidized low-density lipoprotein (oxLDL) receptor (LOX-1) and the GPCR angiotensin II type 1 receptor (AT1) to report a hitherto unidentified mechanism whereby internalization of the GPCR mediates cellular endocytosis of the PRR ligand. Using genetically modified Chinese hamster ovary cells, we found that oxLDL activates Gαi but not the Gαq pathway of AT1 in the presence of LOX-1. Endocytosis of the oxLDL-LOX-1 complex through the AT1-β-arrestin pathway was demonstrated by real-time imaging of the membrane dynamics of LOX-1 and visualization of endocytosis of oxLDL. Finally, this endocytotic pathway involving GPCR kinases (GRKs), β-arrestin, and clathrin is relevant in accumulating oxLDL in human vascular endothelial cells. Together, our findings indicate that oxLDL activates selective G proteins and β-arrestin-dependent internalization of AT1, whereby the oxLDL-LOX-1 complex undergoes endocytosis.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/c18ff51b2f1b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/30eda3476049/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/6e5e6c08c6b5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/d018c7e44c11/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/3c1d8fee63d2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/2a7b062092a9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/2fb106b4e9d3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/c18ff51b2f1b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/30eda3476049/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/6e5e6c08c6b5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/d018c7e44c11/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/3c1d8fee63d2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/2a7b062092a9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/2fb106b4e9d3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/7890409/c18ff51b2f1b/gr6.jpg

相似文献

[1]
The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor.

iScience. 2021-1-21

[2]
Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor.

FASEB J. 2015-8

[3]
Beta-arrestin- and dynamin-dependent endocytosis of the AT1 angiotensin receptor.

Mol Pharmacol. 2001-2

[4]
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J Biol Chem. 1999-10-29

[5]
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Regul Pept. 2004-8-15

[6]
Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells.

Toxicol Appl Pharmacol. 2013-10-19

[7]
Molecular mechanisms of angiotensin II receptor internalization.

J Am Soc Nephrol. 1999-1

[8]
Association of angiotensin II receptor 1 and lectin-like oxidized low-density lipoprotein receptor-1 mediates the cardiac hypertrophy induced by oxidized low-density lipoprotein.

Biochem Biophys Res Commun. 2017-8-12

[9]
ROCK2 associates with lectin-like oxidized LDL receptor-1 and mediates oxidized LDL-induced IL-8 production.

Am J Physiol Cell Physiol. 2010-2-24

[10]
Agonist-induced endocytosis and recycling of the gonadotropin-releasing hormone receptor: effect of beta-arrestin on internalization kinetics.

Mol Endocrinol. 1998-12

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[2]
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[3]
Oxidized low-density lipoprotein potentiates angiotensin II-induced Gq activation through the AT1-LOX1 receptor complex.

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[4]
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Amino Acids. 2024-5-31

[5]
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Sci Rep. 2023-10-27

[6]
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[7]
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[8]
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Int J Mol Sci. 2022-3-20

[9]
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Front Cell Infect Microbiol. 2022

[10]
ATRAP, a receptor-interacting modulator of kidney physiology, as a novel player in blood pressure and beyond.

Hypertens Res. 2022-1

本文引用的文献

[1]
SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis.

Nature. 2019-4-24

[2]
Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations.

Cell. 2019-1-10

[3]
Functional selectivity profiling of the angiotensin II type 1 receptor using pathway-wide BRET signaling sensors.

Sci Signal. 2018-12-4

[4]
Beta-Arrestin1 Prevents Preeclampsia by Downregulation of Mechanosensitive AT1-B2 Receptor Heteromers.

Cell. 2018-11-29

[5]
Designer Approaches for G Protein-Coupled Receptor Modulation for Cardiovascular Disease.

JACC Basic Transl Sci. 2018-8-28

[6]
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.

Physiol Rev. 2018-7-1

[7]
Mechanoactivation of the angiotensin II type 1 receptor induces β-arrestin-biased signaling through Gα coupling.

J Cell Biochem. 2018-1-4

[8]
Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow.

Proc Natl Acad Sci U S A. 2017-9-25

[9]
Prolonged ATR activation induces Ca1.2 channel internalization in rat cardiomyocytes.

Sci Rep. 2017-8-31

[10]
Novel Structural Insights into GPCR-β-Arrestin Interaction and Signaling.

Trends Cell Biol. 2017-6-23

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