Heparan sulfate expression in polarized epithelial cells: The apical sorting of glypican (GPI-anchored proteoglycan) is inversely related to its heparan sulfate content

被引:92
作者
Mertens, G
VanderSchueren, B
vandenBerghe, H
David, G
机构
[1] CATHOLIC UNIV LEUVEN,CTR HUMAN GENET,B-3000 LOUVAIN,BELGIUM
[2] FLANDERS INST BIOTECHNOL,LOUVAIN,BELGIUM
关键词
D O I
10.1083/jcb.132.3.487
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Several processes that occur in the luminal compartments of the tissues are modulated by heparin-like polysaccharides. To identify proteins responsible for the expression of heparan sulfate at the apex of polarized cells, we investigated the polarity of the expression of the cell surface heparan sulfate proteoglycans in CaCo-2 cells. Domain-specific biotinylation of the apical and basolateral membranes of these cells identified glypican, a GPI-linked heparan sulfate proteoglycan, as the major source of apical heparan sulfate. Yet, most of this proteoglycan was expressed at the basolateral surface, an unexpected finding for a glypiated protein. Metabolic labeling and chase experiments indicated that sorting mechanisms, rather than differential turnover, accounted for this bipolar expression of glypican. Chlorate treatment did not affect the polarity of the expression of glypican in CaCo-2 cells, and transfectant MDCK cells expressed wild-type glypican and a syndecan-4/glypican chimera also in an essentially unpolarized fashion. Yet, complete removal of the heparan sulfate glycanation sites from the glypican core protein resulted in the nearly exclusive apical targeting of glypican in the transfectants, whereas two- and one-chain mutant forms had intermediate distributions. These results indicate that glypican accounts for the expression of apical heparan sulfate, but that glycanation of the, core protein antagonizes the activity of the apical sorting signal conveyed by the GPI anchor of this proteoglycan. A possible implication of these findings is that heparan sulfate glycanation may be a determinant of the subcellular expression of glypican. Alternatively, inverse glycanation-apical sorting relationships in glypican may insure near constant deliveries of HS to the apical compartment, or ''active'' GPI-mediated entry of heparan sulfate into apical membrane compartments may require the overriding of this antagonizing effect of the heparan sulfate chains.
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页码:487 / 497
页数:11
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共 45 条
  • [31] REQUIREMENT OF HEPARAN-SULFATE FOR BFGF-MEDIATED FIBROBLAST GROWTH AND MYOBLAST DIFFERENTIATION
    RAPRAEGER, AC
    KRUFKA, A
    OLWIN, BB
    [J]. SCIENCE, 1991, 252 (5013) : 1705 - 1708
  • [32] INTEGRAL AND PERIPHERAL PROTEIN-COMPOSITION OF THE APICAL AND BASOLATERAL MEMBRANE DOMAINS IN MDCK CELLS
    SARGIACOMO, M
    LISANTI, M
    GRAEVE, L
    LEBIVIC, A
    RODRIGUEZBOULAN, E
    [J]. JOURNAL OF MEMBRANE BIOLOGY, 1989, 107 (03) : 277 - 286
  • [33] SAXENA U, 1991, J BIOL CHEM, V266, P17516
  • [34] TRANSPORT OF LIPOPROTEIN-LIPASE ACROSS ENDOTHELIAL-CELLS
    SAXENA, U
    KLEIN, MG
    GOLDBERG, IJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) : 2254 - 2258
  • [35] 5' NUCLEOTIDASE IS SORTED TO THE APICAL DOMAIN OF HEPATOCYTES VIA AN INDIRECT ROUTE
    SCHELL, MJ
    MAURICE, M
    STIEGER, B
    HUBBARD, AL
    [J]. JOURNAL OF CELL BIOLOGY, 1992, 119 (05) : 1173 - 1182
  • [36] LIPID SORTING IN EPITHELIAL-CELLS
    SIMONS, K
    VAN MEER, G
    [J]. BIOCHEMISTRY, 1988, 27 (17) : 6197 - 6202
  • [37] POLARIZED SORTING IN EPITHELIA
    SIMONS, K
    WANDINGERNESS, A
    [J]. CELL, 1990, 62 (02) : 207 - 210
  • [38] HEPARIN-INDUCED OLIGOMERIZATION OF FGF MOLECULES IS RESPONSIBLE FOR FGF RECEPTOR DIMERIZATION, ACTIVATION, AND CELL-PROLIFERATION
    SPIVAKKROIZMAN, T
    LEMMON, MA
    DIKIC, I
    LADBURY, JE
    PINCHASI, D
    HUANG, J
    JAYE, M
    CRUMLEY, G
    SCHLESSINGER, J
    LAX, I
    [J]. CELL, 1994, 79 (06) : 1015 - 1024
  • [39] CEREBROGLYCAN - AN INTEGRAL MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN THAT IS UNIQUE TO THE DEVELOPING NERVOUS-SYSTEM AND EXPRESSED SPECIFICALLY DURING NEURONAL DIFFERENTIATION
    STIPP, CS
    LITWACK, ED
    LANDER, AD
    [J]. JOURNAL OF CELL BIOLOGY, 1994, 124 (1-2) : 149 - 160
  • [40] T-CELL ADHESION INDUCED BY PROTEOGLYCAN-IMMOBILIZED CYTOKINE MIP-1-BETA
    TANAKA, Y
    ADAMS, DH
    HUBSCHER, S
    HIRANO, H
    SIEBENLIST, U
    SHAW, S
    [J]. NATURE, 1993, 361 (6407) : 79 - 82