Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone.
Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.
Yang
Jing
J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Brown
Michael S
MS
Liang
Guosheng
G
Grishin
Nick V
NV
Goldstein
Joseph L
JL
D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D016678:Genome; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment
D002210:Caprylates; D054439:Ghrelin; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D000217:Acyltransferases; C526983:Mboat4 protein, mouse; C031492:octanoic acid