iScience (Feb 2021)
The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor
- Toshimasa Takahashi,
- Yibin Huang,
- Koichi Yamamoto,
- Go Hamano,
- Akemi Kakino,
- Fei Kang,
- Yuki Imaizumi,
- Hikari Takeshita,
- Yoichi Nozato,
- Satoko Nozato,
- Serina Yokoyama,
- Motonori Nagasawa,
- Tatsuo Kawai,
- Masao Takeda,
- Taku Fujimoto,
- Kazuhiro Hongyo,
- Futoshi Nakagami,
- Hiroshi Akasaka,
- Yoichi Takami,
- Yasushi Takeya,
- Ken Sugimoto,
- Herbert Y. Gaisano,
- Tatsuya Sawamura,
- Hiromi Rakugi
Affiliations
- Toshimasa Takahashi
- 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
- Yibin Huang
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Corresponding author
- Go Hamano
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Akemi Kakino
- Department of Molecular Pathophysiology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan
- Fei Kang
- Department of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada
- Yuki Imaizumi
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Hikari Takeshita
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Yoichi Nozato
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Satoko Nozato
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Serina Yokoyama
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Motonori Nagasawa
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Tatsuo Kawai
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Masao Takeda
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Taku Fujimoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Kazuhiro Hongyo
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Futoshi Nakagami
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Hiroshi Akasaka
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Yoichi Takami
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Yasushi Takeya
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Ken Sugimoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Herbert Y. Gaisano
- Department of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada
- Tatsuya Sawamura
- Department of Molecular Pathophysiology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan
- Hiromi Rakugi
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Journal volume & issue
-
Vol. 24,
no. 2
p. 102076
Abstract
Summary: 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.
