Functional UDP-xylose Transport across the Endoplasmic Reticulum/Golgi Membrane in a Chinese Hamster Ovary Cell Mutant Defective in UDP-xylose Synthase

被引:47
作者
Bakker, Hans [1 ]
Oka, Takuji [2 ]
Ashikov, Angel [1 ]
Yadav, Ajit [1 ]
Berger, Monika [1 ]
Rana, Nadia A. [3 ]
Bai, Xiaomei [4 ]
Jigami, Yoshifumi [2 ]
Haltiwanger, Robert S. [3 ]
Esko, Jeffrey D. [4 ]
Gerardy-Schahn, Rita [1 ]
机构
[1] Hannover Med Sch, Zentrum Biochem, D-30625 Hannover, Germany
[2] Natl Inst Adv Ind Sci & Technol, Res Ctr Glycosci, Tsukuba, Ibaraki 3058566, Japan
[3] SUNY Stony Brook, Inst Cell & Dev Biol, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA
[4] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
GROWTH FACTOR-LIKE; GLUCURONIC ACID DECARBOXYLASE; NUCLEOTIDE-SUGAR TRANSPORTER; FUNGUS CRYPTOCOCCUS-NEOFORMANS; HEPARAN-SULFATE BIOSYNTHESIS; PROTEOGLYCAN CORE PROTEIN; SUBSTRATE-SPECIFICITY; XT-II; N-ACETYLGLUCOSAMINYLTRANSFERASE; SUBCELLULAR-LOCALIZATION;
D O I
10.1074/jbc.M804394200
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
In mammals, xylose is found as the first sugar residue of the tetrasaccharide GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, initiating the formation of the glycosaminoglycans heparin/heparan sulfate and chondroitin/dermatan sulfate. It is also found in the trisaccharide Xyl alpha 1-3Xyl alpha 1-3Glc beta 1-O-Ser on epidermal growth factor repeats of proteins, such as Notch. UDP-xylose synthase (UXS), which catalyzes the formation of the UDP-xylose substrate for the different xylosyltransferases through decarboxylation of UDP-glucuronic acid, resides in the endoplasmic reticulum and/or Golgi lumen. Since xylosylation takes place in these organelles, no obvious requirement exists for membrane transport of UDP-xylose. However, UDP-xylose transport across isolated Golgi membranes has been documented, and we recently succeeded with the cloning of a human UDP-xylose transporter (SLC25B4). Here we provide new evidence for a functional role of UDP-xylose transport by characterization of a new Chinese hamster ovary cell mutant, designated pgsI-208, that lacks UXS activity. The mutant fails to initiate glycosaminoglycan synthesis and is not capable of xylosylating Notch. Complementation was achieved by expression of a cytoplasmic variant of UXS, which proves the existence of a functional Golgi UDP-xylose transporter. A similar to 200 fold increase of UDP-glucuronic acid occurred in pgsI-208 cells, demonstrating a lack of UDP-xylose-mediated control of the cytoplasmically localized UDP-glucose dehydrogenase in the mutant. The data presented in this study suggest the bidirectional transport of UDP-xylose across endoplasmic reticulum/Golgi membranes and its role in controlling homeostasis of UDP-glucuronic acid and UDP-xylose production.
引用
收藏
页码:2576 / 2583
页数:8
相关论文
共 52 条
  • [1] Rumi is a CAP10 domain glycosyltransferase that modifies notch and is required for notch signaling
    Acar, Melih
    Jafar-Nejad, Hamed
    Takeuchi, Hideyuki
    Rajan, Akhila
    Ibrani, Dafina
    Rana, Nadia A.
    Pan, Hongling
    Haltiwanger, Robert S.
    Bellen, Hugo J.
    [J]. CELL, 2008, 132 (02) : 247 - 258
  • [2] The human solute carrier gene SLC35B4 encodes a bifunctional nucleotide sugar transporter with specificity for UDP-xylose and UDP-N-acetylglucosamine
    Ashikov, A
    Routier, F
    Fuhlrott, J
    Helmus, Y
    Wild, M
    Gerardy-Schahn, R
    Bakker, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (29) : 27230 - 27235
  • [3] Chinese hamster ovary cell mutants defective in glycosaminoglycan assembly and glucuronosyltransferase I
    Bai, XM
    Wei, G
    Sinha, A
    Esko, JD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) : 13017 - 13024
  • [4] An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation
    Bai, XM
    Esko, JD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (30) : 17711 - 17717
  • [5] An Arabidopsis thaliana cDNA complements the N-acetylglucosaminyltransferase I deficiency of CHO Lec1 cells
    Bakker, H
    Lommen, A
    Jordi, W
    Stiekema, W
    Bosch, D
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 261 (03) : 829 - 832
  • [6] BAME KJ, 1989, J BIOL CHEM, V264, P8059
  • [7] Functional cloning and characterization of a UDP-glucuronic acid decarboxylase:: The pathogenic fungus Cryptococcus neoformans elucidates UDP-xylose synthesis
    Bar-Peled, M
    Griffith, CL
    Doering, TL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (21) : 12003 - 12008
  • [8] Differential regulation of UDP-GlcUA transport in endoplasmic reticulum and in Golgi membranes
    Bossuyt, X
    Blanckaert, N
    [J]. JOURNAL OF HEPATOLOGY, 2001, 34 (02) : 210 - 214
  • [9] Glycosyltransferase activity of fringe modulates notch-delta interactions
    Brückner, K
    Perez, L
    Clausen, H
    Cohen, S
    [J]. NATURE, 2000, 406 (6794) : 411 - 415
  • [10] Biosynthesis of chondroitin and heparan sulfate in Chinese hamster ovary cells depends on xylosyltransferase II
    Cuellar, Karen
    Chuong, Hoa
    Hubbell, Sherry M.
    Hinsdale, Myron E.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (08) : 5195 - 5200