title: O-fucosylation of notch occurs in the endoplasmic reticulum.
abstract: LADII (leukocyte adhesion deficiency type II)/CDGIIc (congenital disorder of glycosylation type IIc) is a rare autosomal recessive disease characterized by leukocyte adhesion deficiency as well as severe neurological and developmental abnormalities. It is caused by mutations in the Golgi GDP-fucose transporter, resulting in a reduction of fucosylated antigens on the cell surface. A recent study using fibroblasts from LADII/CDGIIc patients suggested that although terminal fucosylation of N-glycans is reduced severely, protein O-fucosylation is generally unaffected (Sturla, L., Rampal, R., Haltiwanger, R. S., Fruscione, F., Etzioni, A., and Tonetti, M. (2003) J. Biol. Chem. 278, 26727-26733). A potential explanation for this phenomenon is that enzymes adding O-fucose to proteins localize to cell organelles other than the Golgi apparatus. In this study, we investigated the subcellular localization of protein O-fucosyltransferase 1 (O-FucT-1), which is responsible for adding O-fucose to epidermal growth factor-like repeats. Our analysis reveals that, unlike all other known fucosyltransferases, O-FucT-1 is a soluble protein that localizes to the endoplasmic reticulum (ER). In addition, it appears that O-FucT-1 is retained in the ER by a KDEL-like sequence at its C terminus. Our results also suggest that enzymatic addition of O-fucose to proteins occurs in the ER, suggesting that a novel, ER-localized GDP-fucose transporter may exist. The fact that O-FucT-1 recognizes properly folded epidermal growth factor-like repeats, together with this unique localization, suggests that it may play a role in quality control.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, State University of New York at Stony Brook, Stony Brook, New York 11794-5215, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Robert S
authors.initials: RS
authors.lastname: Haltiwanger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D017510:Protein Folding; D051880:Receptors, Notch
chemical_list: D008565:Membrane Proteins; D051880:Receptors, Notch; D005643:Fucose; D004815:Epidermal Growth Factor; D005647:Fucosyltransferases