New ligands for melanocortin receptors

Kaelin, Christopher B.; Candille, Sophie I.; Yu, Bin; Jackson, Peter K.; Thompson, Darren A.; Nix, Matthew A.; Binkley, Jonathan; Millhauser, Glenn L.; Barsh, Gregory S.

doi:10.1038/ijo.2008.234

Cited by 25 publications

(20 citation statements)

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“…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). …”

Section: An Overview Of the Central Nervous Melanocortin Systemmentioning

confidence: 99%

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

et al. 2017

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Melanocortin neurons conserve body mass in hyper- or hypo-caloric conditions by conveying signals from nutrient sensors into areas of the brain governing appetite and metabolism. In mice, melanocortin-3 receptor (MC3R) deletion alters nutrient partitioning independently of hyperphagia, promoting accumulation of fat over muscle mass. Enhanced rhythms in insulin and insulin-responsive metabolic genes during hypocaloric feeding suggest partial insulin resistance and enhanced lipogenesis. However, exactly where and how MC3Rs affect metabolic control to alter nutrient partitioning is not known. The behavioral phenotypes exhibited by MC3R-deficient mice suggest a contextual role in appetite control. The impact of MC3R-deficiency on feeding behavior when food is freely available is minor. However, homeostatic responses to hypocaloric conditioning involving increased expression of appetite-stimulating (orexigenic) neuropeptides, binge-feeding, food anticipatory activity (FAA), entrainment to nutrient availability and enhanced feeding-related motivational responses are compromised with MC3R-deficiency. Rescuing Mc3r transcription in hypothalamic and limbic neurons improves appetitive responses during hypocaloric conditioning while having minor effects on nutrient partitioning, suggesting orexigenic functions. Rescuing hypothalamic MC3Rs also restores responses of fasting-responsive hypothalamic orexigenic neurons in hypocaloric conditions, suggesting actions that sensitize fasting-responsive neurons to signals from nutrient sensors. MC3R signaling in ventromedial hypothalamic SF1(+ve) neurons improves metabolic control, but does not restore appetitive responses or nutrient partitioning. In summary, desensitization of fasting-responsive orexigenic neurons may underlie attenuated appetitive responses of MC3R-deficient mice in hypocaloric situations. Further studies are needed to identify the specific location(s) of MC3Rs controlling appetitive responses and partitioning of nutrients between fat and lean tissues.

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Section: An Overview Of the Central Nervous Melanocortin Systemmentioning

confidence: 99%

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

et al. 2017

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“…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.…”

Section: Setting the Scene: Human Pigmentation Genetics -The Field Anmentioning

confidence: 99%

Colorful DNA polymorphisms in humans

Liu

Wen

Kayser

2013

Seminars in Cell & Developmental Biology

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a b s t r a c tIn this review article we summarize current knowledge on how variation on the DNA level influences human pigmentation including color variation of iris, hair, and skin. We review recent progress in the field of human pigmentation genetics by focusing on the genes and DNA polymorphisms discovered to be involved in determining human pigmentation traits, their association with diseases particularly skin cancers, and their power to predict human eye, hair, and skin colors with potential utilization in forensic investigations.

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“…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.…”

Section: à4mentioning

confidence: 99%

Digital gene expression for non-model organisms

Hong¹,

Li²,

Schmidt‐Küntzel³

et al. 2011

Genome Res.

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Next-generation sequencing technologies offer new approaches for global measurements of gene expression but are mostly limited to organisms for which a high-quality assembled reference genome sequence is available. We present a method for gene expression profiling called EDGE, or EcoP15I-tagged Digital Gene Expression, based on ultra-highthroughput sequencing of 27-bp cDNA fragments that uniquely tag the corresponding gene, thereby allowing direct quantification of transcript abundance. We show that EDGE is capable of assaying for expression in >99% of genes in the genome and achieves saturation after 6-8 million reads. EDGE exhibits very little technical noise, reveals a large (10 6 ) dynamic range of gene expression, and is particularly suited for quantification of transcript abundance in non-model organisms where a high-quality annotated genome is not available. In a direct comparison with RNA-seq, both methods provide similar assessments of relative transcript abundance, but EDGE does better at detecting gene expression differences for poorly expressed genes and does not exhibit transcript length bias. Applying EDGE to laboratory mice, we show that a loss-of-function mutation in the melanocortin 1 receptor (Mc1r), recognized as a Mendelian determinant of yellow hair color in many different mammals, also causes reduced expression of genes involved in the interferon response. To illustrate the application of EDGE to a non-model organism, we examine skin biopsy samples from a cheetah (Acinonyx jubatus) and identify genes likely to control differences in the color of spotted versus non-spotted regions.

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New ligands for melanocortin receptors

Cited by 25 publications

References 100 publications

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

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

Colorful DNA polymorphisms in humans

Digital gene expression for non-model organisms

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