Evidence for leptin receptor isoforms heteromerization at the cell surface

被引:23
作者
Bacart, Johan
Leloire, Audrey
Levoye, Angelique [2 ]
Froguel, Philippe [3 ]
Jockers, Ralf [4 ,5 ]
Couturier, Cyril [1 ]
机构
[1] Univ Lille 2, Inst Biol Lille 1, CNRS, UMR8090, F-59021 Lille, France
[2] Inst Pasteur, INSERM, U819, F-75724 Paris, France
[3] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London SW7 2AZ, England
[4] Univ Paris 05, CNRS, Inst Cochin, UMR 8104, Paris, France
[5] INSERM, U567, Paris, France
关键词
Bioluminescence resonance energy transfer; LEPR; Heteromerization; Yellow fluorescent Protein for energy transfer; Protein-protein interaction; Obesity; LIGAND-INDEPENDENT DIMERIZATION; OB-R; CYTOPLASMIC DOMAIN; ACTIVATION; IDENTIFICATION; TRANSDUCER;
D O I
10.1016/j.febslet.2010.03.033
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
Leptin mediates its metabolic effects through several leptin receptor (LEP-R) isoforms. In humans, long (LEPRb) and short (LEPRa,c,d) isoforms are generated by alternative splicing. Most of leptin's effects are believed to be mediated by the OB-Rb isoform. However, the role of short LEPR isoforms and the possible existence of heteromers between different isoforms are poorly understood. Using BRET1 and optimized co-immunoprecipitation, we observed LEPRa/b and LEPRb/c heteromers located at the plasma membrane and stabilized by leptin. Given the widespread coexpression of LEPRa and LEPRb, our results suggest that LEPRa/b heteromers may represent a major receptor species in most tissues. Structured summary: MINT-7714817: LEPRb (uniprotkb:P48357-1) physically interacts (MI:0915) with LEPRb (uniprotkb: P48357-1) by anti tag co-immunoprecipitation (MI: 0007) MINT-7714785: LEPRc (uniprotkb:P48357-2) physically interacts (MI: 0915) with LEPRc (uniprotkb: P48357-2) by bioluminescence resonance energy transfer (MI: 0012) MINT-7714951, MINT-7714744: LEPRa (uniprotkb:P48357-3) physically interacts (MI: 0915) with LEPRa (uniprotkb: P48357-3) by bioluminescence resonance energy transfer (MI: 0012) MINT-7714859: LEPRb (uniprotkb: P48357-1) physically interacts (MI: 0915) with LEPRa (uniprotkb: P48357-3) by anti tag co-immunoprecipitation (MI: 0007) MINT-7714885, MINT-7714672: LEPRb (uniprotkb: P48357-1) physically interacts (MI: 0915) with LEPRb (uniprotkb: P48357-1) by bioluminescence resonance energy transfer (MI: 0012) MINT-7714835: LEPRa (uniprotkb: P48357-3) physically interacts (MI: 0915) with LEPRa (uniprotkb: P48357-3) by anti tag co-immunoprecipitation (MI: 0007) MINT-7714914, MINT-7714723, MINT-7714759: LeprB (uniprotkb: P48357-1) physically interacts (MI: 0915) with LEPRa (uniprotkb: P48357-3) by bioluminescence resonance energy transfer (MI: 0012) MINT-7714703, MINT-7714936, MINT-7714772: LEPRb (uniprotkb: P48357-1) physically interacts (MI: 0915) with LEPRc (uniprotkb: P48357-2) by bioluminescence resonance energy transfer (MI: 0012) MINT-7714872: LEPRb (uniprotkb: P48357-1) physically interacts (MI: 0915) with LEPRc (uniprotkb: P48357-2) by anti tag co-immunoprecipitation (MI: 0007) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:2213 / 2217
页数:5
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