New ligands for melanocortin receptors

Abstract

Named originally for their effects on peripheral end organs, the melanocortin system controls a diverse set of physiological processes through a series of five G-protein-coupled receptors and several sets of small peptide ligands. The central melanocortin system plays an essential role in homeostatic regulation of body weight, in which two alternative ligands, a-melanocytestimulating hormone and agouti-related protein, stimulate and inhibit receptor signaling in several key brain regions that ultimately affect food intake and energy expenditure. Much of what we know about the relationship between central melanocortin signaling and body weight regulation stems from genetic studies. Comparative genomic studies indicate that melanocortin receptors used for controlling pigmentation and body weight regulation existed more than 500 million years ago in primitive vertebrates, but that fine-grained control of melanocortin receptors through neuropeptides and endogenous antagonists developed more recently. Recent studies based on dog coat-color genetics revealed a new class of melanocortin ligands, the b-defensins, which reveal the potential for cross talk between the melanocortin and the immune systems.

A Life without Hunger: The Ups (and Downs) to Modulating Melanocortin-3 Receptor Signaling

“…Melanocortin receptor pharmacology is complex, with two antagonists/inverse agonists (AgRP and agouti signaling peptide) and MSH ligands that exhibit varying degrees of receptor specificity (Figure 1B; Cone et al, 1996). Other ligands and cell-surface proteins have been identified that regulate melanocortin signaling (e.g., melanocortin receptor accessory proteins 1 and 2, mahogany, mahoganoid, attractin-like protein, syndecans, ion channels and defensins) (Kaelin et al, 2008; Nix et al, 2013, 2015; Anderson et al, 2016). …”

Colorful DNA polymorphisms in humans

“…1B) illustrates the collaboration patterns between 10 top clusters consisting of 1903 authors representing 29.6% of the field. Some influential authors (only one per cluster is listed here due to space limitation) are listed in the following in alphabetical order together with their respective fields of research: BARSH GS (mammalian pigmentation [1,2]), FISHER DE (melanoma [3]), HEARING VJ (melanogenesis [4]), STURM RA (human pigmentation [5][6][7]), KAYSER M (prediction [8]), PAUS R (hair follicle [9]), REES JL (evolution [10]), SHRIVER MD (evolution [11,12]), SOUFIR N (melanoma [13]), SPRITZ RA (vitiligo [14]). These figures demonstrate the variety of research areas involved in human pigmentation genetics some of which we discuss below.…”

Digital gene expression for non-model organisms

“…Studies of additional cheetah samples will a Expression levels are given as tags per million reads of an EDGE library prepared from RNA of a black spot or yellow background area of cheetah skin. The genes shown here were chosen based on their roles in pigment cell biology; six are well-established melanocyte transcriptional targets downstream from MC1R signaling (Kobayashi et al 1995;Lamoreux et al 1995;Chintala et al 2005;April and Barsh 2006;Le Pape et al 2009); four encode secreted factors that act upstream, either as ligands or to modify ligands of the MC1R Enshell-Seijffers et al 2008;Kaelin et al 2008); and one, MITF, encodes a transcription factor required for melanocyte development (Steingrímsson et al 2006). The expected direction, increase (+) or decrease (À), for expression level change of each gene is given according to when pigment production switches from yellow pheomelanin to black eumelanin.…”