TY - JOUR
T1 - The melanocortin receptors
T2 - Agonists, antagonists, and the hormonal control of pigmentation
AU - Cone, Roger D.
AU - Lu, Dongsi
AU - Koppula, Sandhya
AU - Vage, Dag Inge
AU - Klungland, Helge
AU - Boston, Bruce
AU - Chen, Wenbiao
AU - Orth, David N.
AU - Pouton, Colin
AU - Kesterson, Robert A.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - Molecular cloning experiments have led to the identification and characterization of a family of five receptors for the melanocortin (melanotropic and adrenocorticotropic) peptides. The first two members of the family cloned were the well-characterized melanocyte-stimulating hormone receptor (MSH-R) and adrenocorticotropin receptor (ACTH-R). The three new melanocortin receptors have been termed the MC3-R, MC4-R, and MC5-R. according to the order of their discovery, and little is known at this point concerning their function. Agouti and extension are two genetic loci known to control the amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments. Chromosomal mapping demonstrated that the MSH-R, now termed MC1-R, mapped to extension. Extension was shown to encode the MC1-R, and mutations in the MC1-R are responsible for the different pigmentation phenotypes caused by this locus. Functional variants of the MC1-R, originally characterized in the mouse, have now also been identified in the guinea pig and cow. Dominant constitutive mutants of the MC1-R are responsible for causing dark black coat colors while recessive alleles result in yellow or red coat colors. Agouti, a secreted 108 amino acid peptide produced within the hair follicle, acts on follicular melanocytes to inhibit α-MSH-induced eumelanin production. Experiments demonstrate that agouti is a high-affinity antagonist, acting at the MC1-R to block α-MSH stimulation of adenylyl cyclase, the effector through which ct-MSH induces eumelanin synthesis. The MC1-R is thus a unique bifunctionally controlled receptor, activated by α-MSH and antagonized by agouti, both contributing to the variability seen in mammalian coat colors. The variable tan and black coat color patterns seen in the German Shepherd, for example, can now be understood on the molecular level as the interaction of a number of extension and agouti alleles encoding variably functioning receptors and a differentially expressed antagonist of the receptor, respectively.
AB - Molecular cloning experiments have led to the identification and characterization of a family of five receptors for the melanocortin (melanotropic and adrenocorticotropic) peptides. The first two members of the family cloned were the well-characterized melanocyte-stimulating hormone receptor (MSH-R) and adrenocorticotropin receptor (ACTH-R). The three new melanocortin receptors have been termed the MC3-R, MC4-R, and MC5-R. according to the order of their discovery, and little is known at this point concerning their function. Agouti and extension are two genetic loci known to control the amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments. Chromosomal mapping demonstrated that the MSH-R, now termed MC1-R, mapped to extension. Extension was shown to encode the MC1-R, and mutations in the MC1-R are responsible for the different pigmentation phenotypes caused by this locus. Functional variants of the MC1-R, originally characterized in the mouse, have now also been identified in the guinea pig and cow. Dominant constitutive mutants of the MC1-R are responsible for causing dark black coat colors while recessive alleles result in yellow or red coat colors. Agouti, a secreted 108 amino acid peptide produced within the hair follicle, acts on follicular melanocytes to inhibit α-MSH-induced eumelanin production. Experiments demonstrate that agouti is a high-affinity antagonist, acting at the MC1-R to block α-MSH stimulation of adenylyl cyclase, the effector through which ct-MSH induces eumelanin synthesis. The MC1-R is thus a unique bifunctionally controlled receptor, activated by α-MSH and antagonized by agouti, both contributing to the variability seen in mammalian coat colors. The variable tan and black coat color patterns seen in the German Shepherd, for example, can now be understood on the molecular level as the interaction of a number of extension and agouti alleles encoding variably functioning receptors and a differentially expressed antagonist of the receptor, respectively.
UR - http://www.scopus.com/inward/record.url?scp=0029706921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029706921&partnerID=8YFLogxK
M3 - Article
C2 - 8701084
AN - SCOPUS:0029706921
SN - 0079-9963
VL - 51
SP - 287
EP - 317
JO - Recent progress in hormone research
JF - Recent progress in hormone research
ER -