Inhibition of melanocortin-4 receptor dimerization by substitutions in intracellular loop 2

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Inhibition of melanocortin-4 receptor dimerization by substitutions in intracellular loop 2.

Obesity is one of the most challenging global health problems. One key player in energy homeostasis is the melanocortin-4 receptor (MC4R), which is a family A G-protein-coupled receptor (GPCR). It has recently been shown that MC4R has the capacity to form homo- or heterodimers. Dimerization of GPCRs is of great importance for signaling regulation, with major pharmacological implications. Unfort...

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Melanocortin 4 receptor becomes an ACTH receptor by coexpression of melanocortin receptor accessory protein 2.

Melanocortin 2 receptor (MC2R) is the only canonical ACTH receptor. Its functional expression requires the presence of an accessory protein, known as melanocortin receptor 2 accessory protein 1 (MRAP1). The vertebrate genome exhibits a paralogue gene called MRAP2, which is duplicated in zebrafish (MRAP2a and MRAP2b), although its function remains unknown. In this paper, we demonstrate that MRAP...

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Expression of Melanocortin 4 Receptor mRNA in Male Rat Hypothalamus During Chronic Stress

The effects of chronic stress and glucocorticoids receptor antagonist (RU486) on expression of melanocortin 4 receptor (MC4R) mRNA in arcuate nucleus (ARC) of male rats were evaluated. In this study, adult male Sprague Dawley rats were placed into four groups (n=6/group) stress, RU486, stress/RU486, and control groups. In stress group, the rats were restrained, 1 h/day, for 12 days. In RU486 gr...

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Anti-melanocortin-4 receptor autoantibodies in obesity.

BACKGROUND The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. METHODS The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluate...

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G-protein Coupled Receptor Dimerization

A growing body of evidence suggests that GPCRs exist and function as dimers or higher oligomers. The evidence for GPCR dimerization comes from biochemical, biophysical and functional studies. In addition, researchers have shown the occurrence of heterodimerization between different members of the GPCR family. Two receptors can interact with each other to make a dimer through their extracellular...

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ژورنال

عنوان ژورنال: Journal of Molecular Endocrinology

سال: 2013

ISSN: 0952-5041,1479-6813

DOI: 10.1530/jme-13-0061