scholarly journals The melanocortin 1 receptor is the principal mediator of the effects of agouti signaling protein on mammalian melanocytes

2001 ◽  
Vol 114 (5) ◽  
pp. 1019-1024 ◽  
Author(s):  
Z.A. Abdel-Malek ◽  
M.C. Scott ◽  
M. Furumura ◽  
M.L. Lamoreux ◽  
M. Ollmann ◽  
...  
Keyword(s):  
Coat Color ◽  
Wild Type Mouse ◽  
Tyrosinase Activity ◽  
Loss Of Function ◽  
Wild Type ◽  
Melanocortin 1 Receptor ◽  
Signaling Protein ◽  
Melanocyte Stimulating Hormone ◽  
Related Proteins ◽  
Stimulating Hormone

The agouti gene codes for agouti signaling protein (ASP), which is temporally expressed in wild-type mouse follicular melanocytes where it induces pheomelanin synthesis. Studies using purified full-length agouti signaling protein has shown that it competes with (α)-melanocyte stimulating hormone for binding to the melanocortin 1 receptor. We have investigated whether ASP binds exclusively to the melanocortin 1 receptor expressed on mouse melanocytes in primary culture, or additionally activates a receptor that has not been identified yet. We have compared the responses of congenic mouse melanocytes derived from C57 BL/6J-E(+)/E(+), e/e, or E(so)/E(so) mice to (alpha)-MSH and/or ASP. E(+)/E(+) melanocytes express the wild-type melanocortin 1 receptor, e/e melanocytes express a loss-of-function mutation in the melanocortin 1 receptor that results in a yellow coat color, and E(so)/E(so) is a mutation that causes constitutive activation of the melanocortin 1 receptor and renders melanocytes unresponsive to (alpha)-melanocyte stimulating hormone. Mouse E(+)/E(+) melanocytes, but not e/e or E(so)/E(so) melanocytes, respond to agouti signaling protein with decreased basal tyrosinase activity, and reduction in levels of tyrosinase and tyrosinase-related proteins 1 and 2. Only in E(+)/E(+) melanocytes does agouti signaling protein abrogate the stimulatory effects of (alpha)-melanocyte stimulating hormone on cAMP formation and tyrosinase activity. These results indicate that a functional melanocortin 1 receptor is obligatory for the response of mammalian melanocytes to agouti signaling protein.

Effect of α-melanocyte-stimulating hormone on tyrosinase activity in hair follicular and epidermal melanocytes of the mouse

1988 ◽  
Vol 119 (3) ◽  
pp. 517-522 ◽  
Author(s):  
P. Seechurn ◽  
S. A. Burchill ◽  
A. J. Thody
Keyword(s):  
Tyrosinase Activity ◽  
In Vitro Experiments ◽  
Dorsal Skin ◽  
Wild Type ◽  
Melanocyte Stimulating Hormone ◽  
Tyrosinase Expression ◽  
In Vivo Administration ◽  
Agouti Gene

ABSTRACT In this study, the effect of α-MSH on tyrosinase activity was compared in epidermal and hair follicular melanocytes of mice. It had no effect on epidermal tyrosinase activity in dorsal skin from neonatal non-agouti black mice (C57BL/6J) in both in-vivo and in-vitro experiments. Theophylline and 8-bromocyclic (c)AMP were similarly without effect in in-vitro experiments. In-vivo administration of α-MSH and theophylline for 7 days was also without effect on epidermal tyrosinase activity in ear skin of adult non-agouti mice, and the same was true for α-MSH in wild-type agouti mice. Activation of the epidermal melanocytes in the non-agouti and wild-type agouti mice with ultraviolet radiation also failed to bring about a response to α-MSH and to theophylline in the case of the former. No tyrosinase activity was detected in the epidermis of viable yellow mice (C3H-HeAvy), but, as shown previously, tyrosinase activity was present in the hair follicle when the hair was actively growing and was increased in those mice given either α-MSH or theophylline. α-MSH and theophylline had no such effects on hair follicular tyrosinase activity in the non-agouti mice. The present results suggest that α-MSH- and cAMP-dependent mechanisms have little or no importance in the regulation of tyrosinase expression in mouse epidermal melanocytes. α-MSH may, however, regulate tyrosinase expression in hair follicular melanocytes, but even in these melanocytes its action may be restricted to mice that express the agouti gene. J. Endocr. (1988) 119, 517–522

scholarly journals Three novel mutations in ASIP associated with black fibre in alpacas (Vicugna pacos)

2011 ◽  
Vol 149 (4) ◽  
pp. 529-538 ◽  
Author(s):  
N. L. FEELEY ◽  
S. BOTTOMLEY ◽  
K. A. MUNYARD
Keyword(s):  
Amino Acids ◽  
Regulatory Region ◽  
Loss Of Function ◽  
Coding Region ◽  
Contributing Factors ◽  
Novel Mutations ◽  
Melanocortin 1 Receptor ◽  
Melanocyte Stimulating Hormone ◽  
Vicugna Pacos ◽  
Probable Loss

SUMMARYThe coding region of the alpaca Agouti signalling protein (ASIP) gene was sequenced. It was determined to be 402 nucleotides long and code for a protein that is 133 amino acids long. Eight mutations were identified in a sample of 15 alpaca, five in the coding region and three in the introns flanking the exons. In silico analysis showed that three of the five mutations in the coding sequence, c.325_381del57, c.292C>T and c.353G>A are probable loss-of-function mutations. The three mutations were strongly associated with black fibre colour, with 0·90 of black alpacas in the current study having two copies of one or another of the mutations. However, not all black animals displayed the putative ‘aa’ genotype, and almost half of the non-black animals did display that genotype. Contributing factors such as regulatory region mutations, interactions of ASIP with melanocortin-1 receptor (MC1R) and α-melanocyte stimulating hormone (α-MSH), the effect of dilution genes and subjective phenotype assignment are discussed. These mutations will allow alpaca breeders to select for or against black, but they do not explain all black phenotypes in this species.

scholarly journals A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

2005 ◽  
Vol 187 (2) ◽  
pp. 293-302 ◽  
Author(s):  
Jennifer D Spencer ◽  
Bhaven Chavan ◽  
Lee K Marles ◽  
Sobia Kauser ◽  
Hartmut Rokos ◽  
...  
Keyword(s):  
Opiate Receptor ◽  
Melanocortin 1 Receptor ◽  
Melanocyte Stimulating Hormone ◽  
Receptor Signal ◽  
Major Player ◽  
Key Enzyme ◽  
Μ Opiate Receptor ◽  
Inhibition Reaction ◽  
Stimulating Hormone

The human skin holds the full machinery for pro-opiomelanocortin processing. The α-melanocyte-stimulating hormone (α-MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the β-endorphin/μ-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (6BH4) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both α- and β-MSH. It was also shown earlier that 7BH4, the isomer of 6BH4, is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH4 is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 × 10−6 M. Determination of β-MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH4/tyrosinase inhibitor complex by β-MSH, whereas α-MSH failed to do so. Furthermore, we show intra-melanosomal l-dopa formation from dopachrome by 7BH4 in a concentration range up to 134 × 10−6 M. Based on these results, we propose a new receptor-independent mechanism in the control of tyrosinase/melanogenesis by β-MSH and the pterin 7BH4.

scholarly journals Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation is associated with partial recessive red phenotypes in dog

2020 ◽  
Author(s):  
Heidi Anderson ◽  
Leena Honkanen ◽  
Päivi Ruotanen ◽  
Julia Mathlin ◽  
Jonas Donner
Keyword(s):  
Citizen Science ◽  
Coat Color ◽  
Allelic Variation ◽  
Wild Type ◽  
Melanocortin 1 Receptor ◽  
Phenotype Analysis ◽  
Genotype Screening ◽  
Dominant Black ◽  
Novel Allele

Abstract Background The Melanocortin 1 Receptor (MC1R) plays a central role in regulation of coat color determination in dogs and is commonly referred to as the “E (extension) Locus”. Allelic variation of the MC1R gene is associated with coat color phenotypes EM (melanistic mask), EG (grizzle/domino) and e1–3 (recessive red) in dogs. In addition, a previous study of archeological dog specimens over 10,000 years of age identified a variant p.R301C in the MC1R gene that may have influenced coat color of early dogs. Results Commercial genotyping of 11,726 dog samples showed the R301C variant of the MC1R gene was present in 34 breeds or breed varieties, at an allele frequency of 1.48% in the tested population. We detected no linkage disequilibrium between R301C and other tested alleles of the E locus. Based on current convention we propose that R301C should be considered a novel allele of the E locus, which we have termed eA for “e ancient”. Phenotype analysis of owner-provided dog pictures reveals eA allele has an impact on coat color and is recessive to wild type E and dominant to the e alleles. In dominant black (KB/*) dogs it can prevent the expression of the K locus, and the expressed coat color is solely determined by the A locus. In the absence of dominant black, eA/eA and eA/e genotypes result in the coat color patterns referred to in their respective breed communities as domino in Alaskan Malamute and other Spitz breeds, grizzle in Chihuahua, and pied in Beagle. Conclusions This study demonstrates a large genotype screening effort to identify the frequency and distribution of the MC1R R301C variant, one of the earliest mutations captured by canine domestication, and citizen science empowered characterization of its impact on coat color.

scholarly journals Sequence Characterization of theMC1RGene in Yak (Poephagus grunniens) Breeds with Different Coat Colors

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Shi-Yi Chen ◽  
Yi Huang ◽  
Qing Zhu ◽  
Luca Fontanesi ◽  
Yong-Gang Yao ◽  
...  
Keyword(s):  
Coat Color ◽  
Extracellular Loop ◽  
Wild Type ◽  
Coding Region ◽  
Functional Effect ◽  
Nucleotide Substitutions ◽  
Melanocortin 1 Receptor ◽  
Sequence Characterization ◽  
Potential Association

Melanocortin 1 receptor (MC1R) gene plays a key role in determining coat color in several species, including the cattle. However, up to now there is no report regarding theMC1Rgene and the potential association of its mutations with coat colors in yak (Poephagus grunniens). In this study, we sequenced the encoding region of theMC1Rgene in three yak breeds with completely white (Tianzhu breed) or black coat color (Jiulong and Maiwa breeds). The predicted coding region of the yakMC1Rgene resulted of 954 bp, the same to that of the wild-type cattle sequence, with >99% identity. None of the mutation events reported in cattle was found. Comparing the yak obtained sequences, five nucleotide substitutions were detected, which defined three haplotypes (EY1,EY2, andEY3). Of the five mutations, two, characterizing theEY1haplotype, were nonsynonymous substitutions (c.340C>A and c.871G>A) causing amino acid changes located in the first extracellular loop (p.Q114K) and in the seventh transmembrane region (p.A291T).In silicoprediction might indicate a functional effect of the latter substitution. However, all three haplotypes were present in the three yak breeds with relatively consistent frequency distribution, despite of their distinguished coat colors, which suggested that there was no across-breed association between haplotypes or genotypes and black/white phenotypes, at least in the investigated breeds. Other genes may be involved in affecting coat color in the analyzed yaks.

The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color determination

1995 ◽  
Vol 6 (9) ◽  
pp. 636-639 ◽  
Author(s):  
H. Klungland ◽  
D. I. Vage ◽  
L. Gomez-Raya ◽  
S. Adalsteinsson ◽  
S. Lien
Keyword(s):  
Coat Color ◽  
Melanocyte Stimulating Hormone ◽  
Color Determination ◽  
Stimulating Hormone

EFFECTS OF α-MELANOCYTE-STIMULATING HORMONE AND [8-ARGININE]-VASOTOCIN UPON MELANOGENESIS IN HAIR FOLLICLE MELANOCYTES IN VITRO

1981 ◽  
Vol 91 (3) ◽  
pp. 501-507 ◽  
Author(s):  
ANN LOGAN ◽  
BRIAN WEATHERHEAD
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Tyrosinase Activity ◽  
Arginine Vasotocin ◽  
Melanin Production ◽  
Potency Ratio ◽  
Melanin Biosynthesis ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

α-Melanocyte-stimulating hormone (α-MSH) has been shown to act directly on the mammalian melanocyte in short-term cultures of hair follicles obtained from the Siberian hamster. Melanogenesis was stimulated through an increase in tyrosinase activity which resulted in an increase in melanin production. The response of hair follicle melanocytes to α-MSH occurred only in follicles taken from moulting animals, implying that they show a discontinuous expression of MSH receptors during the hair follicle growth cycle. Synthetic 1–24 ACTH had no effect on melanogenesis regardless of whether the follicles came from moulting or non-moulting animals. The pineal peptide, [8-arginine]-vasotocin (AVT), inhibited melanin production without a concomitant decrease in tyrosinase activity. In this respect AVT resembled melatonin, although AVT showed a potency ratio of less than half on a molar basis. The action of AVT, like that of melatonin, must ultimately be on some post-tyrosinase step in melanin biosynthesis. In these hair follicle melanocytes AVT seems to bind to specific receptors since neither of the closely related peptides, oxytocin and [8-arginine]-vasopressin, displayed any activity in our culture system.

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