Evidence for leptin receptor isoforms heteromerization at the cell surface

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.