Carbohydrate deficient glycoprotein syndrome type IV:: deficiency of dolichyl-P-Man:Man5GlcNAc2-PP-dolichyl mannosyltransferase

被引:108
作者
Körner, C
Knauer, R
Stephani, U
Marquardt, T
Lehle, L
von Figura, K
机构
[1] Univ Gottingen, Biochem Abt 2, D-37073 Gottingen, Germany
[2] Univ Regensburg, Lehrstuhl Zellbiol & Pflanzenphysiol, D-93053 Regensburg, Germany
[3] Klin & Poliklin Kinderheilkunde, D-48149 Munster, Germany
[4] Univ Kiel, Klin Neuropaediat, Kiel, Germany
关键词
ALG3; gene; carbohydrate deficient glycoprotein syndrome; dolichyl-P-Man : Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase;
D O I
10.1093/emboj/18.23.6816
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Type IV of the carbohydrate deficient glycoprotein syndromes (CDGS) is characterized by microcephaly, severe epilepsy, minimal psychomotor development and partial deficiency of sialic acids in serum glycoproteins. Here we show that the molecular defect in the index patient is a missense mutation in the gene encoding the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol, The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs. N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites. The mannosyltransferase is the structural and functional orthologue of the Saccharomyces cerevisiae ALG3 gene.
引用
收藏
页码:6816 / 6822
页数:7
相关论文
共 24 条
[1]   Cloning and characterization of the ALG3 gene of Saccharomyces cerevisiae [J].
Aebi, M ;
Gassenhuber, J ;
Domdey, H ;
Heesen, ST .
GLYCOBIOLOGY, 1996, 6 (04) :439-444
[2]   APPLICATIONS OF HIGH-EFFICIENCY LITHIUM-ACETATE TRANSFORMATION OF INTACT YEAST-CELLS USING SINGLE-STRANDED NUCLEIC-ACIDS AS CARRIER [J].
GIETZ, RD ;
SCHIESTL, RH .
YEAST, 1991, 7 (03) :253-263
[3]   A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic [J].
Imbach, T ;
Burda, P ;
Kuhner, P ;
Wevers, RA ;
Aebi, M ;
Berger, EG ;
Hennet, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6982-6987
[4]   CARBOHYDRATE-DEFICIENT GLYCOPROTEIN-SYNDROME TYPE-II - A DEFICIENCY IN GOLGI LOCALIZED N-ACETYL-GLUCOSAMINYLTRANSFERASE-II [J].
JAEKEN, J ;
SCHACHTER, H ;
CARCHON, H ;
DECOCK, P ;
CODDEVILLE, B ;
SPIK, G .
ARCHIVES OF DISEASE IN CHILDHOOD, 1994, 71 (02) :123-127
[5]   SIALIC ACID-DEFICIENT SERUM AND CEREBROSPINAL-FLUID TRANSFERRIN IN A NEWLY RECOGNIZED GENETIC SYNDROME [J].
JAEKEN, J ;
VANEIJK, HG ;
VANDERHEUL, C ;
CORBEEL, L ;
EECKELS, R ;
EGGERMONT, E .
CLINICA CHIMICA ACTA, 1984, 144 (2-3) :245-247
[6]   YEAST SACCHAROMYCES-CEREVISIAE SELECTABLE MARKERS IN PUC18 POLYLINKERS [J].
JONES, JS ;
PRAKASH, L .
YEAST, 1990, 6 (05) :363-366
[7]   NORMAL N-OLIGOSACCHARYLTRANSFERASE ACTIVITY IN FIBROBLASTS FROM PATIENTS WITH CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME [J].
KNAUER, R ;
LEHLE, L ;
HANEFELD, F ;
VONFIGURA, K .
JOURNAL OF INHERITED METABOLIC DISEASE, 1994, 17 (05) :541-544
[8]   The oligosaccharyltransferase complex from Saccharomyces cerevisiae -: Isolation of the OST6 gene, its synthetic interaction with OST3, and analysis of the native complex [J].
Knauer, R ;
Lehle, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (24) :17249-17256
[9]  
KNAUER R, 1999, FEBS LETT, V311, P83
[10]   Abnormal synthesis of mannose 1-phosphate derived carbohydrates in carbohydrate-deficient glycoprotein syndrome type I fibroblasts with phosphomannomutase deficiency [J].
Körner, C ;
Lehle, L ;
von Figura, K .
GLYCOBIOLOGY, 1998, 8 (02) :165-171