Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum.
Wnt is a family of cysteine-rich secreted glycoproteins, which controls the fate and behavior of the cells in multicellular organisms. In the absence of Drosophila segment polarity gene porcupine (porc), which encodes an endoplasmic reticulum (ER) multispanning transmembrane protein, the N-glycosylation of Wingless (Wg), one of Drosophila Wnt family, is impaired. In contrast, the ectopic expression of porc stimulates the N-glycosylation of both endogenously and exogenously expressed Wg. The N-glycosylation of Wg in the ER occurs posttranslationally, while in the presence of dithiothreitol, it efficiently occurs cotranslationally. Thus, the cotranslational disulfide bond formation of Wg competes with the N-glycosylation by an oligosaccharyl transferase complex. Porc binds the N-terminal 24-amino acid domain (residues 83-106) of Wg, which is highly conserved in the Wnt family and stimulates the N-glycosylation at surrounding sites. Porc is also necessary for the processing of Drosophila Wnt-3/5 in both embryos and cultured cells. Thus, Porc binds the N-terminal specific domain of the Wnt family and stimulates its posttranslational N-glycosylation by anchoring them at the ER membrane possibly through acylation.
Tanaka
Kimiko
K
Graduate Program for Regulation of Biological Signals, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601 Japan.
Kitagawa
Yasuo
Y
Kadowaki
Tatsuhiko
T
D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004220:Disulfides / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D019476:Insect Proteins / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D051155:Wnt1 Protein
D017931:DNA Primers; D004220:Disulfides; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C103067:por protein, Drosophila; C074622:wg protein, Drosophila