Intercellular Transfer of GPRC5B via Exosomes Drives HGF-Mediated Outward Growth

被引:37
作者
Kwon, Sang-Ho [1 ]
Liu, Kathleen D. [2 ]
Mostov, Keith E. [1 ,3 ,4 ]
机构
[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
关键词
ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; FACTOR RECEPTOR; C-MET; CELLS; PROTEINS; VESICLES; MICROVESICLES; ACTIVATION; EXPRESSION;
D O I
10.1016/j.cub.2013.12.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
How cells communicate during development and regeneration is a critical question. One mechanism of intercellular communication is via exosomes, extracellular vesicles that originate by the fusion of multivesicular endosomes with the plasma membrane [1-8]. To model exosome-based intercellular communication, we used Madin-Darby canine kidney (MDCK) cell cysts grown in 3D gels of extracellular matrix, which form tubules in response to hepatocyte growth factor (HGF). We report that GPRC5B, an orphan G protein coupled receptor, is in exosomes produced by HGF-treated cysts and released into the cyst lumen. Exosomal GPRC5B is taken up by nearby cells and together with HGF promotes extracellular signal-regulated kinase 1/2 (ERK1/2) activation and tubulogenesis, even under conditions where tubulogenesis would otherwise not occur. Recovery from injury, such as acute kidney injury (AKI), often recapitulates developmental processes. Here, we show that GPRC5B is elevated in urinary exosomes from patients with AKI. Our results elucidate how GPRC5B is carried by exosomes and augments HGF-induced morphogenesis. The unexpected role of exosomes in transporting GPRC5B between cells during morphogenesis and the ability of GPRC5B to predict the disease state of AKI elucidate a novel mechanism for intercellular communication during development and repair.
引用
收藏
页码:199 / 204
页数:6
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