A biochemical function for attractin in agouti-induced pigmentation and obesity.
Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (A(y)) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus. Mouse attractin (Atrn) is a widely expressed transmembrane protein whose loss of function in mahogany (Atrn(mg-3J)/ Atrn(mg-3J)) mutant mice blocks the pleiotropic effects of A(y). Here we demonstrate in transgenic, biochemical and genetic-interaction experiments that attractin is a low-affinity receptor for agouti protein, but not Agrp, in vitro and in vivo. Additional histopathologic abnormalities in Atrn(mg-3J)/Atrn(mg-3J) mice and cross-species genomic comparisons indicate that Atrn has multiple functions distinct from both a physiologic and an evolutionary perspective.
He
L
L
Departments of Pediatric, Stanford University School of Medicine, Stanford, California, USA.
Gunn
T M
TM
Bouley
D M
DM
Lu
X Y
XY
Watson
S J
SJ
Schlossman
S F
SF
Duke-Cohan
J S
JS
Barsh
G S
GS
D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D000818:Animals; D002490:Central Nervous System / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005816:Genetic Complementation Test; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006200:Hair Color / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics*; D010446:Peptide Fragments / Q000378:metabolism; D010858:Pigmentation / Q000235:genetics*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance; D019076:Transgenes / Q000235:genetics
D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; C515183:a protein, mouse