Alternative G protein coupling and biased agonism: new insights into melanocortin-4 receptor signalling.
The melanocortin-4 receptor (MC4R) is a prototypical G protein-coupled receptor (GPCR) that plays a considerable role in controlling appetite and energy homeostasis. Signalling initiated by MC4R is orchestrated by multiple agonists, inverse agonism and by interactions with accessory proteins. The exact molecular events translating MC4R signalling into its physiological role, however, are not fully understood. This review is an attempt to summarize new aspects of MC4R signalling in the context of its recently discovered alternative G protein coupling, and to give a perspective on how future research could improve our knowledge about the intertwining molecular mechanisms that are responsible for the regulation of energy homeostasis by the melanocortin system.
Breit
Andreas
A
Walther-Straub-Institut für Pharmakologie und Toxikologie, Goethestrasse 33, Ludwig-Maximilians-Universität München, 80336 München, Germany. andreas.breit@lrz.uni-muenchen.de
Büch
Thomas R H
TR
Boekhoff
Ingrid
I
Solinski
Hans Jürgen
HJ
Damm
Ellen
E
Gudermann
Thomas
T
D000818:Animals; D019204:GTP-Binding Proteins / Q000819:agonists* / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D044105:Receptor, Melanocortin, Type 4; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins