Evidence for leptin receptor isoforms heteromerization at the cell surface

Bacart, Johan; Leloire, Audrey; Levoye, Angélique; Froguel, Philippe; Jockers, Ralf; Couturier, Cyril

doi:10.1016/j.febslet.2010.03.033

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Volume 584, Issue 11 , Pages 2213-2217, 3 June 2010

Evidence for leptin receptor isoforms heteromerization at the cell surface

Edited by Michael R. Bubb

Johan Bacart
- Unité Mixte de Recherche 8090, Centre National de la Recherche Scientifique, Université Lille 2, Lille, France
Audrey Leloire
- Unité Mixte de Recherche 8090, Centre National de la Recherche Scientifique, Université Lille 2, Lille, France
Angélique Levoye
- Inserm U819, Institut Pasteur, Paris, France
Philippe Froguel
- Unité Mixte de Recherche 8090, Centre National de la Recherche Scientifique, Université Lille 2, Lille, France
- Genomic Medicine, Hammersmith Hospital, Imperial College London, UK
Ralf Jockers
- Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France
- Inserm U567, Paris, France
Cyril Couturier
- Unité Mixte de Recherche 8090, Centre National de la Recherche Scientifique, Université Lille 2, Lille, France
- Correspendence to: Cyril Couturier, UMR8090, CNRS, Université Lille 2, Institut de Biologie de Lille, 1 rue du Professeur Calmette, BP 245, 59021 Lille cedex, France. Fax: +33 3 2087 10 31.

Received 25 November 2009; received in revised form 10 March 2010; accepted 18 March 2010. published online 29 March 2010.

Abstract

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)

Abbreviations: BRET, bioluminescence resonance energy transfer, Luc, luciferase, YPet, yellow fluorescent protein for energy transfer

Keywords: Bioluminescence resonance energy transfer, LEPR, Heteromerization, Yellow fluorescent Protein for energy transfer, Protein–protein interaction, Obesity