Dimerization of adiponectin receptor 1 is inhibited by adiponectin

被引:35
作者
Kosel, David [1 ]
Heiker, John T. [1 ]
Juhl, Cathleen [1 ]
Wottawah, Cornelia M. [1 ]
Blueher, Matthias [2 ]
Moerl, Karin [1 ]
Beck-Sickinger, Annette G. [1 ]
机构
[1] Univ Leipzig, Fac Biosci Pharm & Psychol, Inst Biochem, D-04103 Leipzig, Germany
[2] Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany
关键词
Adiponectin; Adiponectin receptor; Receptor dimerization; Bimolecular fluorescence complementation; BIMOLECULAR FLUORESCENCE COMPLEMENTATION; PROTEIN-COUPLED RECEPTOR; RESONANCE ENERGY-TRANSFER; FATTY-ACID OXIDATION; LIVING CELLS; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; SKELETAL-MUSCLE; VISUALIZATION; KINASE;
D O I
10.1242/jcs.057919
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
AdipoR1 and AdipoR2 are newly discovered members of the huge family of seven-transmembrane receptors, but both receptors are structurally and functionally different from G-protein-coupled receptors. Little is known about the oligomerization of the AdipoRs. Here, we show the presence of endogenous AdipoR1 dimers in various cell lines and human muscle tissue. To directly follow and localize the dimerization, we applied bimolecular fluorescence complementation (BiFC) in combination with flow cytometry. We visualized and quantified AdipoR1 homodimers in HEK293 cells. Moreover, we identified a GxxxG dimerization motif in the fifth transmembrane domain of the AdipoR1. By mutating both glycine residues to phenylalanine or glutamic acid, we were able to modulate the dimerization of AdipoR1, implicating a role for the GxxxG motif in AdipoR1 dimerization. Furthermore, we tested whether the AdipoR1 ligand adiponectin had any influence on receptor dimerization. Interestingly, we found that adiponectin decreases the receptor dimerization in a concentration-dependent manner. This effect is mainly mediated by segments of the collagen-like domain of full-length adiponectin. Accordingly, this is the first direct read-out signal of adiponectin at the AdipoR1 receptor, which revealed the involvement of specific amino acids of both the receptor and the ligand to modulate the quaternary structure of the AdipoR1.
引用
收藏
页码:1320 / 1328
页数:9
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