Gene structure of the goldfish agouti-signaling protein: a putative role in the dorsal-ventral pigment pattern of fish.

One of the most successful chromatic adaptations in vertebrates is the dorsal-ventral pigment pattern in which the dorsal skin is darkly colored, whereas the ventrum is light. In fish, the latter pattern is achieved because a melanization inhibition factor inhibits melanoblast differentiation and supports iridophore proliferation in the ventrum. In rodents, the patterned pigmentation results from regional production of the agouti-signaling protein (ASP). This peptide controls the switch between production of eumelanin and pheomelanin by antagonizing alphaMSH effects on melanocortin receptor (MCR) 1 in the melanocytes. In addition, ASP inhibits the differentiation and proliferation of melanoblast. Thus, the mammalian ASP may be homologous to the poikilotherm melanization inhibition factor. By screening of a genomic library, we deduced the amino acid sequence of goldfish ASP. The ASP gene is a four-exon gene spanning 3097 bp that encodes a 125-amino acid precursor. Northern blot analysis identified two different ASP mRNAs in ventral skin of red- and black-pigmented and albino fish, but no expression levels were observed in the dorsal skin of the same fish. The dorsal-ventral expression polarity was also detected in both black dorsally pigmented fish and albino fish. Pharmacological studies demonstrate that goldfish ASP acts as a melanocortin antagonist at Fugu MC1R and goldfish MC4R. In addition, goldfish ASP inhibited Nle4, D-Phe7-MSH-stimulated pigment dispersion in medaka melanophores. Our studies support agouti signaling protein as the melanization inhibition factor, a key factor in the development of the dorsal-ventral pigment pattern in fish.

[1]  Robert Fredriksson,et al.  The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. , 2004, Molecular biology and evolution.

[2]  Yunhan Hong,et al.  Mitf expression is sufficient to direct differentiation of medaka blastula derived stem cells to melanocytes , 2003, Development.

[3]  R. Cone,et al.  Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio , 2003, Endocrine.

[4]  H. Schiöth,et al.  Molecular cloning, characterization and brain mapping of the melanocortin 5 receptor in the goldfish , 2003, Journal of neurochemistry.

[5]  R. Peter,et al.  Endogenous melanocortin antagonist in fish: structure, brain mapping, and regulation by fasting of the goldfish agouti-related protein gene. , 2003, Endocrinology.

[6]  H. Schiöth,et al.  Molecular cloning, pharmacological characterization, and brain mapping of the melanocortin 4 receptor in the goldfish: involvement in the control of food intake. , 2003, Endocrinology.

[7]  S. Aspengren,et al.  Noradrenaline- and melatonin-mediated regulation of pigment aggregation in fish melanophores. , 2003, Pigment cell research.

[8]  A. Zuasti.  Melanization stimulating factor (MSF) and melanization inhibiting factor (MIF) in the integument of fish , 2002, Microscopy research and technique.

[9]  J. Lister,et al.  Development of pigment cells in the zebrafish embryo , 2002, Microscopy research and technique.

[10]  M. Sugimoto.  Morphological color changes in fish: Regulation of pigment cell density and morphology , 2002, Microscopy research and technique.

[11]  M. Goda,et al.  Mechanism by which an elevation of extracellular glucide concentration induces pigment aggregation in medaka melanophores , 2002, Microscopy research and technique.

[12]  G. Barsh,et al.  Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity. , 2002, Biochemistry.

[13]  Stephen L. Johnson,et al.  The evolution of morphological complexity in zebrafish stripes. , 2002, Trends in genetics : TIG.

[14]  K. Wakamatsu,et al.  Molecular and phenotypic analysis of 25 recessive, homozygous-viable alleles at the mouse agouti locus. , 2002, Genetics.

[15]  G. Barsh,et al.  High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein. , 2001, Biochemistry.

[16]  Stephen L. Johnson,et al.  How the zebrafish gets its stripes. , 2001, Developmental biology.

[17]  G. Barsh,et al.  Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts , 2001, Developmental dynamics : an official publication of the American Association of Anatomists.

[18]  Stanley J. Watson,et al.  A biochemical function for attractin in agouti-induced pigmentation and obesity , 2001, Nature Genetics.

[19]  D. Larhammar,et al.  Molecular evolution of the neuropeptide Y (NPY) family of peptides: cloning of three NPY-related peptides from the sea bass (Dicentrarchus labrax) , 2000, Regulatory Peptides.

[20]  R. Kelsh,et al.  Genetic analysis of melanophore development in zebrafish embryos. , 2000, Developmental biology.

[21]  V. Hearing,et al.  Bioactive motifs of agouti signal protein. , 2000, Experimental cell research.

[22]  R. Cone,et al.  The Central Melanocortin System and Energy Homeostasis , 1999, Trends in Endocrinology & Metabolism.

[23]  W. Wilkison,et al.  An agouti mutation lacking the basic domain induces yellow pigmentation but not obesity in transgenic mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  G. Barsh,et al.  Down-regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in XenopusMelanophores* , 1999, The Journal of Biological Chemistry.

[25]  G. Millhauser,et al.  NMR structure of a minimized human agouti related protein prepared by total chemical synthesis , 1999, FEBS letters.

[26]  M. Tota,et al.  Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors. , 1999, Biochemistry.

[27]  V. Katta,et al.  Determination of disulfide structure in agouti-related protein (AGRP) by stepwise reduction and alkylation. , 1998, Biochemistry.

[28]  D. Fisher,et al.  Involvement of Microphthalmia in the Inhibition of Melanocyte Lineage Differentiation and of Melanogenesis by Agouti Signal Protein* , 1998, The Journal of Biological Chemistry.

[29]  G. Barsh,et al.  Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. , 1997, Science.

[30]  I. Gantz,et al.  Molecular Basis for the Interaction of [Nle4,d-Phe7]Melanocyte Stimulating Hormone with the Human Melanocortin-1 Receptor (Melanocyte α-MSH Receptor)* , 1997, The Journal of Biological Chemistry.

[31]  J. Shutter,et al.  Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. , 1997, Genes & development.

[32]  W. Wilkison,et al.  Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors. , 1997, Biochemistry.

[33]  Victor J. Hruby,et al.  Role of melanocortinergic neurons in feeding and the agouti obesity syndrome , 1997, Nature.

[34]  C. Nüsslein-Volhard,et al.  Zebrafish pigmentation mutations and the processes of neural crest development. , 1996, Development.

[35]  J. Newton,et al.  The amphibian melanization inhibiting factor (MIF) blocks the alpha-MSH effect on mouse malignant melanocytes. , 1996, Pigment cell research.

[36]  N. Copeland,et al.  Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein. , 1996, Genetics.

[37]  L. Siracusa,et al.  Mechanisms for the pleiotropic effects of the agouti gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[38]  N. Copeland,et al.  Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. , 1995, Genetics.

[39]  Richard P. Woychik,et al.  Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor , 1994, Nature.

[40]  G. Barsh,et al.  Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[41]  L. Stubbs,et al.  The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein. , 1993, Genes & development.

[42]  G. Barsh,et al.  Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. , 1993, Genes & development.

[43]  R. Woychik,et al.  Molecular characterization of the mouse agouti locus , 1992, Cell.

[44]  J. T. Bagnara,et al.  Intrinsic pigment-cell stimulating activity in the catfish integument. , 1992, Pigment cell research.

[45]  J. T. Bagnara,et al.  Stimulation of cultured iridophores by amphibian ventral conditioned medium. , 1990, Pigment cell research.

[46]  J. T. Bagnara,et al.  Control of melanoblast differentiation in amphibia by alpha-melanocyte stimulating hormone, a serum melanization factor, and a melanization inhibiting factor. , 1989, Pigment cell research.

[47]  H. Ide,et al.  A ventrally localized inhibitor of melanization in Xenopus laevis skin. , 1988, Developmental biology.

[48]  H. Okayama,et al.  Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. , 1988, BioTechniques.

[49]  S. Ohno,et al.  Diploid-tetraploid relationship among old-world members of the fish family Cyprinidae , 1967, Chromosoma.

[50]  D. I. Våge,et al.  The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. , 1996, Recent progress in hormone research.

[51]  J. H. Law,et al.  Evidence that MIF plays a role in the development of pigmentation patterns in the frog. , 1995, Developmental biology.

[52]  A. Eberle,et al.  Biologically active monoiodinated alpha-MSH derivatives for receptor binding studies using human melanoma cells. , 1991, Journal of receptor research.