"P01 HL70295"
Dotaz
Zobrazit nápovědu
Dolichol is an obligate carrier of glycans for N-linked protein glycosylation, O-mannosylation, and GPI anchor biosynthesis. cis-prenyltransferase (cis-PTase) is the first enzyme committed to the synthesis of dolichol. However, the proteins responsible for mammalian cis-PTase activity have not been delineated. Here we show that Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man. Moreover, we describe a family with a congenital disorder of glycosylation caused by a loss of function mutation in the conserved C terminus of NgBR-R290H and show that fibroblasts isolated from patients exhibit reduced dolichol profiles and enhanced accumulation of free cholesterol identically to fibroblasts from mice lacking NgBR. Mutation of NgBR-R290H in man and orthologs in yeast proves the importance of this evolutionarily conserved residue for mammalian cis-PTase activity and function. Thus, these data provide a genetic basis for the essential role of NgBR in dolichol synthesis and protein glycosylation.
- MeSH
- bodová mutace MeSH
- dolichol metabolismus MeSH
- genový knockout MeSH
- glykosylace MeSH
- kultivované buňky MeSH
- lidé MeSH
- metabolické nemoci genetika metabolismus MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- myši MeSH
- receptory buněčného povrchu chemie genetika metabolismus MeSH
- Saccharomyces cerevisiae - proteiny chemie genetika metabolismus MeSH
- Saccharomyces cerevisiae chemie genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- transferasy chemie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- cis-prenyl transferase MeSH Prohlížeč
- dolichol MeSH
- Nogo-B receptor, mouse MeSH Prohlížeč
- NUS1 protein, human MeSH Prohlížeč
- receptory buněčného povrchu MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- transferasy MeSH
