Proteoglycans are widely expressed in animal cells. Interactions between negatively charged glycosaminoglycan chains and molecules such as growth factors are essential for differentiation of cells during development and maintenance of tissue organisation. We propose that glycosaminoglycan chains play a role in targeting of proteoglycans to their proper cellular or extracellular location. The variability seen in glycosaminoglycan chain structure from cell type to cell type, which is acquired by use of particular Ser-Gly sites in the protein core, might therefore be important for post-synthesis sorting. This links regulation of glycosaminoglycan synthesis to the post-Golgi fate of proteoglycans.

Aikawa
J.
,
Esko
J. D.
(
1999
).
Molecular cloning and expression of a third member of the heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferase family.
J. Biol. Chem
274
,
2690
2695
Almeida
R.
,
Levery
S. B.
,
Mandel
U.
,
Kresse
H.
,
Schwientek
T.
,
Bennett
E. P.
,
Clausen
H.
(
1999
).
Cloning and expression of a proteoglycan UDP-galactose:-xylose 1, 4-galactosyltransferase I.
J. Biol. Chem
274
,
26165
26171
Alonso
M. A.
,
Fan
L.
,
Alarcon
B.
(
1997
).
Multiple sorting signals determine apical localization of a nonglycosylated integral membrane protein.
J. Biol. Chem
272
,
30748
30752
Aspberg
A.
,
Binkert
B.
,
Rouslahti
E.
(
1995
).
The versican C-type lectin domain recognizes the adhesion protein tenascin-R.
Proc. Nat. Acad. Sci. USA
92
,
10590
10594
Bai
X.
,
Esko
J. D.
(
1996
).
An animal cell mutant defective in heparan sulfate hexuronic acid 2–0-sulfation.
J. Biol. Chem
271
,
17711
17717
Bai
X.
,
Wei
G.
,
Esko
J. D.
(
1999
).
Chinese hamster ovary cell mutants defective in glycosaminoglycan assembly and glucuronosyltransferase I.
J. Biol. Chem
274
,
13017
13024
Baker
J. R.
,
Cifonelli
J. A.
,
Roden
L.
(
1975
).
The linkage of corneal keratan sulfate to protein.
Connect. Tissue Res
3
,
149
156
Barthel
A.
,
Nickel
W.
,
Tonko
C.
,
Soling
H. D.
(
1995
).
Sorting and budding of cinstitutive secretory vesicles in hepatocytes and hepatoma cells.
Advan. Enzyme Regul
35
,
283
292
Benting
J. H.
,
Rietveld
A. G.
,
Simons
K.
(
1999
).
N-Glycans mediate the apical sorting of a GPI-anchored, raft associated protein in Madin-Darby canine kidney cells.
J. Cell Biol
146
,
313
320
Berninsone
P.
,
Hirschberg
C. B.
(
1998
).
Heparan sulfate/heparin N-deacetylase/N-sulfotransferase. The N-sulfotransferase activity domain is at the carboxyl half of the holoenzyme.
J. Biol. Chem
273
,
25556
25559
Bonfanti
L.
,
Mironov
A.
Jr.
,
Martinez-Menarguez
J. A.
,
Martella
O.
,
Fusella
A.
,
Baldassarre
M.
,
Buccione
R.
,
Geuze
H. J.
,
Mironov
A. A.
,
Luini
A.
(
1998
).
Procollagen traverses the Golgi stack without leaving the lumen of cisternae: Evidence for cisternal maturation.
Cell
95
,
993
1003
Bourdon
M. A.
,
Krusius
T.
,
Campbell
S.
,
Schwartz
N. B.
,
Ruoslahti
E.
(
1987
).
Identification and synthesis of a recognition signal for the attachment of glycosaminoglycans to proteins.
Proc. Nat. Acad. Sci. USA
84
,
3194
3198
Brändli
A. W.
,
Hansson
G. C.
,
Rodriguez-Boulan
E.
,
Simons
K.
(
1988
).
A polarized epithelial cell mutant deficient in translocation of UDP-galactose into the Golgi complex.
J. Biol. Chem
263
,
16283
16290
Brinkmann
T.
,
Weilke
C.
,
Kleesiek
K.
(
1997
).
Recognition of acceptor proteins by UDP-D-xylose proteoglycan core protein beta-D-xylosyltransferase.
J. Biol. Chem
272
,
11171
11175
Brion
C.
,
Miller
S. G.
,
Moore
H. P.
(
1992
).
Regulated and constitutive secretion. Differential effects of protein synthesis arrest on transport of glycosaminoglycan chains to the two secretory pathways.
J. Biol. Chem
267
,
1477
1483
Calabro
A.
,
Hascall
V.
(
1994
).
Differential effects of brefeldin A on chondroitin sulfate and hyaluronan synthesis in rat chondrosarcoma cells.
J. Biol. Chem
269
,
22764
22770
Cambiazo
V.
,
Inestrosa
N. C.
(
1990
).
Proteoglycan production in Drosophila egg development: effect of beta-D-xyloside on proteoglycan synthesis and larvae motility.
Comp. Biochem. Physiol
97
,
307
314
Campbell
A. G.
,
Fessler
L. I.
,
Salo
T.
,
Fessler
J. H.
(
1987
).
Papilin: a Drosophila proteoglycan-like sulfated glycoprotein from basement membranes.
J. Biol. Chem
262
,
17605
17612
Caplan
M. J.
,
Stow
J. L.
,
Newman
A. P.
,
Madri
J.
,
Anderson
H. C.
,
Farquhar
M. G.
,
Palade
G. E.
,
Jamieson
J. D.
(
1987
).
Dependence on pH of polarized sorting of secreted proteins.
Nature
329
,
632
635
Castle
A. M.
,
Castle
J. D.
(
1998
).
Enhanced glycosylation and sulfation of secretory proteoglycans is coupled to the expression of a basic secretory protein.
Mol. Cell Biol
9
,
575
583
Cheng
F.
,
Heinegard
D.
,
Fransson
L.
,
Bayliss
M.
,
Bielicki
J.
,
Hopwood
J.
,
Yoshida
K.
(
1996
).
Variations in the chondroitin sulfate-protein linkage region of aggrecans from bovine nasal and human articular cartilages.
J. Biol. Chem
271
,
28572
28580
Dietrich
C. P.
,
Nader
H. B.
,
Bounassisi
V.
,
Colburn
P.
(
1988
).
Inhibition of synthesis of heparan sulfate by selenate: possible dependence on sulfation for chain polymerization.
FASEB J
2
,
56
59
Dolan
M.
,
Horchar
T.
,
Rigatti
B.
,
Hassel
J. R.
(
1997
).
Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis.
J. Biol. Chem
272
,
4316
4322
Dours-Zimmermann
M. T.
,
Zimmermann
D.
(
1994
).
A novel glycosaminoglycan attachment domain identified in two alternative splice variants of human versican.
J. Biol. Chem
269
,
32992
32998
Eriksson
I.
,
Sandbäck
D.
,
Ek
B.
,
Lindahl
U.
(
1993
).
cDNA cloning of mouse mastocytoma glucosaminyl N-Deacetylase/N-sulfotransferase, an enzyme involved in the synthesis of heparin.
J. Biol. Chem
269
,
10438
10443
Esko
J. D.
,
Stewart
T. E.
,
Taylor
W. H.
(
1985
).
Animal cell mutants defective in glycosaminoglycan biosynthesis.
Proc. Nat. Acad. Sci. USA
82
,
3197
3201
Esko
J. D.
,
Weinke
J. L.
,
Taylor
W. H.
,
Ekborg
G.
,
Roden
L.
,
Anantharamaiah
G.
,
Gawish
A.
(
1987
).
Inhibition of chondroitin and heparan sulfate biosynthesis in chinese hamster ovary cell mutants defective in galactosyltransferase I.
J. Biol. Chem
262
,
12189
12195
Etchison
J. R.
,
Srikrishna
G.
,
Freeze
H. H.
(
1995
).
A novel method to co-localize glycosaminoglycan core-oligosaccharides glycosyltransferases in rat liver Golgi. Co-localization of galactosyltransferase I with a sialyltransferase.
J. Biol. Chem
270
,
756
764
Fedarko
N. S.
,
Conrad
H. E.
(
1986
).
A unique heparan sulfate in the nuclei of hepatocytes: Structural changes with the growth state of cells.
J. Cell Biol
102
,
587
599
Fiedler
K.
,
Parton
R. G.
,
Kellner
R.
,
Etzold
T.
,
Simons
K.
(
1994
).
VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in epithelial cells.
EMBO J
13
,
1729
1740
Forsberg
E.
,
Pejler
G.
,
Ringvall
M.
,
Lunderius
C.
,
Tomasini-Johansson
,
Kusche-Gullberg
M.
,
Eriksson
I.
,
Ledin
J.
,
Hellman
L.
,
Kjellen
L.
(
1999
).
Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme.
Nature
400
,
773
776
Fransson
L. Å.
,
Silverberg
I.
,
Carlstedt
I.
(
1985
).
Structure of theheparan sulfate-protein linkage region. Demonstration of the sequence galactosyl-galactosyl-xylose-2-phosphate.
J. Biol. Chem
260
,
14722
14726
Fransson
L. Å
(
1987
).
Structure and function of proteoglycans.
Trends Biochem. Sci
12
,
406
411
Fransson
L. A.
,
Karlsson
P.
,
Schmidtchen
A.
(
1992
).
Effects of cycloheximide, brefeldin A, suramin, heparin and primaquine on proteoglycan and glycosaminoglycan biosynthesis in human embryonic skin fibroblasts.
Biochim. Biophys. Acta
1137
,
287
97
Fritz
T. A.
,
Gabb
M. M.
,
Wei
G.
,
Esko
J. D.
(
1994
).
Two N-acetylglucosaminyltransferases catalyze the biosynthesis of heparan sulfate.
J. Biol. Chem
269
,
28809
28814
Fritz
T. A.
,
Agrawal
P. K.
,
Esko
J. D.
,
Krishna
N. R.
(
1997
).
Partial purification and substrate specificity of heparan sulfate alpha-N-acetylglucosaminyltransferase I: synthesis, NMR spectroscopic characterization and in vitro assays of two aryl tetrasaccharides.
Glycobiology
7
,
587
595
Fullekrug
J.
,
Scheiffele
P.
,
Simons
K.
(
1999
).
VIP36 localisation to the early secretory pathway.
J. Cell Sci
112
,
2813
2821
Glick
B. S.
,
Malhotra
V.
(
1999
).
The curious state of the Golgi apparatus.
Cell
95
,
883
889
Greenfield
B.
,
Wang
W. C.
,
Marquardt
H.
,
Piepkorn
M.
,
Wolff
E. A.
,
Aruffo
A.
,
Bennett
K. L.
(
1999
).
Characterization of the heparan sulfate and chondroitin sulfate assembly sites in CD44.
J. Biol. Chem
274
,
2511
2517
Greve
H.
,
Kresse
H.
(
1988
).
Secretion of unphosphorylated and phosphorylated xyloside-induced glycosaminoglycan chains.
Glycoconjugate J
5
,
175
183
Guillen
E.
,
Hirschberg
C. B.
(
1995
).
Transport of adenosine triphosphate into endoplasmic reticulum proteoliposomes.
Biochemistry
34
,
5472
5476
Grimes
M.
,
Kelly
R. B.
(
1992
).
Intermediates in the constitutive and regulated secretory pathways released in vitro from semi-intact cells.
J. Cell Biol
117
,
539
549
Guillen
E.
,
Abeijon
C.
,
Hirschberg
C. B.
(
1998
).
Mammalian Golgi apparatus UDP-N-acetylglucosamine transporter: molecular cloning by phenotypic correction of a yeast mutant.
Proc. Nat. Acad. Sci. USA
95
,
7888
7892
Gut
A.
,
Kappeler
F.
,
Hyka
N.
,
Balda
M. S.
,
Hauri
H. P.
,
Matter
K.
(
1998
).
Carbohydrate-mediated Golgi to cell surface transport and apical targeting of membrane proteins.
EMBO J
17
,
1919
1929
Habuchi
H.
,
Kobayashi
M.
,
Kimata
K.
(
1998
).
Molecular characterization and expression of heparan-sulfate 6-sulfotransferase.
J. Biol. Chem
273
,
9208
9213
Halberg
D. F.
,
Proulx
G.
,
Doege
K.
,
Yamada
Y.
,
Drickamer
K.
(
1988
).
A segment of the cartilage proteoglycan has lectin-like activity.
J. Biol. Chem
263
,
9486
9490
Hashimoto
Y.
,
Orellana
A.
,
Gil
G.
,
Hirschberg.
C. B.
(
1992
).
Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase.
J. Biol. Chem
267
,
15744
15750
Hirschberg
C. B.
,
Snider
M. D.
(
1987
).
Topography of glycosylation in the rough endoplasmic reticulum and Golgi apparatus.
Annu. Rev. Biochem
56
,
63
87
Hirschberg
C. B.
,
Robbins
P. W.
,
Abeijon
C.
(
1998
).
Transporters of nucleotide sugars, ATP and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus.
Annu. Rev. Biochem
67
,
49
69
Huang
C.
,
Sali
A.
,
Stevens
R. L.
(
1998
).
Regulation and function of mast cell proteases in inflammation.
J. Clin. Immunol
18
,
169
183
Humphries
D. E.
,
Sullivan
B. M.
,
Aleixo
M. D.
,
Stow
J. L.
(
1997
).
Localiztion of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network.
Biochem. J
325
,
351
357
Humphries
D. E.
,
Lanciotti
J.
,
Karlinsky
J. B.
(
1998
).
CDNA cloning, genomic organization and chromosomal localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase-2.
Biochem. J
332
,
303
307
Humphries
D. E.
,
Wong
G. W.
,
Friend
D. S.
,
Gurish
M. F.
,
Qiu
W.-T.
,
Huang
C.
,
Sharpe
A. H.
,
Stevens
R. L.
(
1999
).
Heparin is essential for the storage of specific granule proteases in mast cells.
Nature
400
,
769
772
Iozzo
R.
(
1998
).
Matrix proteoglycans: From molecular design to cellular function.
Annu. Rev. Biochem
67
,
609
652
Ishida
N.
,
Miura
N.
,
Yoshioka
S.
,
Kawakita
M.
(
1996
).
Molecular cloning and characterization of a novel isoform of the human UDP-galactose transporter and of related complementary DNAs belonging to the nucleotide-sugar transporter gene family [Rapid communication].
J. Biochem
120
,
1074
1078
Ishihara
M.
,
Fedarko
N. S.
,
Conrad
H. E.
(
1986
).
Transport of heparan sulfate into the nuclei of hepatocytes.
J. Biol. Chem
261
,
13575
13580
Kakuta
Y.
,
Sueyoshi
T.
,
Negishi
M.
,
Pedersen
L. C.
(
1999
).
Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1.
J. Biol. Chem
274
,
10673
10676
Kawakita
M.
,
Ishida
N.
,
Miura
N.
,
Sun-Wada
G. H.
,
Yoshioka
S.
(
1998
).
Nucleotid sugar transporters: elucidation of their molecular identity and its implication for future studies.
J. Biochem
123
,
777
785
Kawashima
H.
,
Li
Y. F.
,
Watanabe
N.
,
Hirose
J.
,
Hirose
M.
,
Miyasaka
M.
(
1999
).
Identification and characterization of ligands for L-selectin in the kidney. I. Versican, a large chondroitin sulfate proteoglycan, is a ligand for L-selectin.
Int. Immunol
11
,
393
405
Kearns
A. E.
,
Campbell
S. C.
,
Westley
J.
,
Schwartz
N. B.
(
1991
).
Initiation of chondroitin sulfate biosynthesis: a kinetic analysis of UDP-D-xylose: core protein beta-D-xylosyltransferase.
Biochemistry
30
,
7477
7483
Kearns
A. E.
,
Vertel
B. M.
,
Schwartz
N. B.
(
1993
).
Topography of glycosylation and UDP-xylose production.
J. Biol. Chem
268
,
11097
11104
Keller
P.
,
Simons
K.
(
1997
).
Post-Golgi biosynthetic trafficking.
J. Cell Sci
110
,
3001
3009
Kimura
N.
,
Mitsuoka
C.
,
Kanamori
A.
,
Hiraiwa
N.
,
Uchimura
K.
,
Muramatsu
T.
,
Tamatani
T.
,
Kansas
G. S.
,
Kannagi
R.
(
1999
).
Reconstitution of functional L-selectin ligands on a cultured human endothelial cell line by cotransfection of1-3 fucosyltransferase VII and newly cloned GlcNAc: 6-sulfotransferase cDNA.
Proc. Nat. Acad. Sci. USA
96
,
4530
4535
Kingsley
D. M.
,
Kozarsky
K. F.
,
Hobbie
L.
,
Krieger
M.
(
1986
).
Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal/UDP-GalNAc 4-epimerase deficient mutant.
Cell
44
,
749
759
Kitagawa
H.
,
Tanaka
Y.
,
Tsuchida
K.
,
Goto
F.
,
Ogawa
T.
,
Lidholt
K.
,
Lindahl
U.
,
Sugahara
K.
(
1995
).
N-acetylgalactosamine (GalNAc) transfer to the common carbohydrate-protein linkage region of sulfated glycosaminoglycans. Identification of UDP-GalNAc:chondro-oligosaccharide alpha-N-acetylgalactosaminyltransferase in fetal bovine serum.
J. Biol. Chem
270
,
22190
22195
Kitagawa
H.
,
Tone
Y.
,
Tamura
J.
,
Neumann
K. W.
,
Ogawa
T.
,
Oka
S.
,
Kawasaki
T.
,
Sugahara
K.
(
1998
).
Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans.
J. Biol. Chem
273
,
6615
6618
Kitagawa
H.
,
Kano
Y.
,
Shimakawa
H.
,
Ogawa
T.
,
Okabe
H.
,
Sugahara
K.
(
1999
).
Identification and characterization of a novel UDP-GalNAc:GlcAbeta-R alpha 1, 4-N-acetylgalactosaminyltransferase from a human sarcoma cell line.
Glycobiology
9
,
697
703
Kjellen
L.
,
Lindahl
U.
(
1991
).
Proteoglycans: structures and interactions.
Annu. Rev. Biochem
60
,
443
475
Kobayashi
M.
,
Sugumaran
G.
,
Liu
J.
,
Shworak
N. W.
,
Silbert
J. E.
,
Rosenberg
R. D.
(
1999
).
Molecular cloning and characterization of a human uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate.
J. Biol. Chem
274
,
10474
10480
Kohda
D.
,
Morton
C. J.
,
Parkar
A. A.
,
Hatanaka
H.
,
Inagaki
F. M.
,
Campbell
I. D.
,
Day
A. J.
(
1996
).
Solution structure of the link module: a hyaluronan-binding domain involved in the extracellular matrix stability and cell migration.
Cell
86
,
767
775
Kolset
S. O.
,
Vuong
T. T.
,
Prydz
K.
(
1999
).
Apical secretion of chondroitin sulphate in polarized Madin-Darby canine kidney (MDCK) cells.
J. Cell Sci
112
,
1797
1801
Kreuger
J.
,
Prydz
K.
,
Pettersson
R. F.
,
Lindahl
U.
,
Salmivirta
M.
(
1999
).
Characterization of fibroblast growth factor 1 binding heparan sulfate domain.
Glycobiology
9
,
723
729
Li
J.-P.
,
Hagner-McWhirther
Å.
,
Kjellen
,
Palgi
J.
,
Jalkanen
M.
,
Lindahl
U.
(
1997
).
Biosynthesis of heparin/heparan sulfate.
J. Biol. Chem
272
,
28158
28163
Li
Y.-F.
,
Kawashima
H.
,
Watanabe
W.
,
Miyasaka
M.
(
1999
).
Identification and characterization of ligands for L-selectin in the kidney. II. Expression of chondroitin sulfate and heparan sulfate proteoglycans reactive with L-selectin.
FEBS Lett
444
,
201
205
Lidholt
K.
,
Riesenfeld
J.
,
Jacobsson
K. G.
,
Feingold
D. S.
,
Lindahl
U.
(
1988
).
Biosynthesis of heparin. Modulation of polysaccharide chain length in a cell-free system.
Biochem. J
254
,
571
578
Lidholt
K.
,
Kjellen
L.
,
Lindahl
U.
(
1989
).
Biosynthesis of heparin.
Biochem. J
261
,
999
1007
Lidholt
K.
,
Lindahl
U.
(
1992
).
Biosynthesis of heparin.
Biochem. J
287
,
21
29
Lidholt
K.
,
Weinke
J. L.
,
Kiser
C. S.
,
Lugemwa
F. N.
,
Bame
K. J.
,
Cheifetz
S.
,
Massague
J.
,
Lindahl
U.
,
Esko
J. D.
(
1992
).
A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis.
Proc. Nat. Acad. Sci
89
,
2267
2271
Lind
T.
,
Lindahl
U.
,
Lidholt
K.
(
1993
).
Biosynthesis of heparin/heparan sulfate. Characterization of a 70 kDa protein catalyzing both the D-glucuronosyl-and the N-acetyl-D-glucosaminyltransferase reactions.
J. Biol. Chem
268
,
20705
20708
Lind
T.
,
Tufaro
F.
,
McCormick
C.
,
Lindahl
U.
,
Lidholt
K.
(
1998
).
The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.
J. Biol. Chem
273
,
26265
26268
Lippincott-Schwartz
J.
,
Donaldson
J. G.
,
Schweizer
A.
,
Berger
E. G.
,
Hauri
H. P.
,
Yuan
L. C.
,
Klausner
R. D.
(
1990
).
Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway.
Cell
60
,
821
836
Lo
A. C.
,
Thinakaran
G.
,
Slunt
H. H.
,
Sisodia
S. S.
(
1995
).
Metabolism of the amyloid precursor-like protein 2 in MDCK cells. Polarized trafficking occurs independent of the chondroitin sulfate glycosaminoglycan chain.
J. Biol. Chem
270
,
12641
12645
Lohmander
L. S.
,
De
L. S.
,
Nilsson
B.
,
Hascall
V. C.
,
Caputo
C. B.
,
Kimura
J. H.
,
Heinegard
D.
(
1980
).
Oligosaccharides on proteoglycans from the swarm rat chondrosarcoma.
J. Biol. Chem
255
,
6084
6091
Lohmander
L. S.
,
Shinomura
T.
,
Hascall
V. C.
,
Kimura
J. H.
(
1989
).
Xylosyl transfer to the core protein precursor of the rat chondrosarcoma proteoglycan.
J. Biol. Chem
264
,
18775
18780
Lutzelschwab
C.
,
Pejler
G.
,
Aveskogh
M.
,
Hellman
L.
(
1997
).
Secretory granule proteases in rat mast cells. Cloning of 10 different serine proteases and carboxypeptidase A from various rat mast cell populations.
J. Exp. Med
185
,
13
29
Mandon
E. C.
,
Milla
M. E.
,
Kempner
E.
,
Hirschberg
C. B.
(
1994
).
Purification of the Golgi adenosine 3-phosphate 5 -phosphosulfate transporter, a homodimer within the membrane.
Proc. Nat. Acad. Sci. USA
91
,
10707
10711
McCormick
C.
,
Leduc
Y.
,
Martindale
D.
,
Mattison
K.
,
Esford
L. E.
,
Dyer
A. P.
,
Tufaro
F.
(
1998
).
The putative tumor suppressor EXT1 alters the expression of cell-surface heparan sulfate.
Nature Genet
19
,
158
161
Miettinen
H. M.
,
Edwards
S. N.
,
Jalkanen
M.
(
1994
).
Analysis of transport and targeting of syndecan-1: effect of cytoplasmic tail deletions.
Mol. Biol. Cell
5
,
1325
1339
Mertens
G.
,
Van der Schueren
B.
,
van den Berghe
H.
,
David
G.
(
1996
).
Heparan sulfate expression in polarized epithelial cells: the apical sorting of glypican (GPI-anchored proteoglycan) is inversely related to its heparan sulfate content.
J. Cell Biol
132
,
487
497
Mironov
A. A.
,
Luini
A.
,
Buccione
R.
(
1998
).
Constitutive transport between the trans-Golgi network and the plasma membrane according to the maturation model. A hypothesis.
FEBS Lett
440
,
99
102
Miura
N.
,
Ishida
N.
,
Hoshino
M.
,
Yamauchi
M.
,
Hara
T.
,
Ayusawa
D.
,
Kawakita
M.
(
1996
).
Human UDP-galactose translocator: molecularcloning of a complementary DNA that complements the genetic defect of a mutant cell line deficient in UDP-galactose translocator.
J. Biochem
120
,
236
241
Miura
R.
,
Aspberg
A.
,
Ethell
I. M.
,
Hagihara
K.
,
Schnaar
R. L.
,
Rouslahti
E.
,
Yamaguchi
Y.
(
1999
).
The proteoglycan lectin domain binds sulfated cell surface glycolipids and promotes cell adhesion.
J. Biol. Chem
274
,
11431
11438
Moses
J.
,
Oldberg
A.
,
Cheng
F.
,
Fransson
L. A.
(
1997
).
Biosynthesis of the proteoglycan decorin. Transient 2-phosphorylation of xylose during formation of the trisaccharide linkage region.
Eur. J. Biochem
248
,
521
526
Moses
J.
,
Oldberg
Å.
,
Fransson
L. Å
(
1999
).
Initiation of galactosaminoglycan biosynthesis. Separate galactosylation and dephosphorylation pathways for phosphoxylosylated decorin protein and exogenous xyloside.
Eur. J. Biochem
260
,
879
884
Nadanaka
S.
,
Kitagawa
H.
,
Goto
F.
,
Tamura
J.-I.
,
Neumann
K. W.
,
Ogawa
T.
,
Sugahara
K.
(
1999
).
Involvement of the core protein in the first-N-acetylgalactosamine transfer to the glycosaminoglycan-protein linkage-region tetrasaccharide and in the subsequent polymerization: the critical determining step for chondroitin sulphate biosynthesis.
Biochem. J
340
,
353
357
Naso
M. F.
,
Zimmermann
D.
,
Iozzo
R.
(
1994
).
Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter.
J. Biol. Chem
269
,
32999
3008
Needham
L. K.
,
Schnaar
R. L.
(
1993
).
The HNK-1 reactive sulfoglucuronyl glycolipids are ligands for L-selectin and P-selectin but not E-selectin.
Proc. Nat. Acad. Sci. USA
90
,
1359
1363
Nickel
W.
,
Huber
L. A.
,
Kahn
R. A.
,
Kipper
N.
,
Barthel
A.
,
Fasshauer
D.
,
Söling
H. D.
) (
1994
).
ADP ribosylation factor and a 14-kD polypeptide are associated with heparan sulfate-carrying post-trans-Golgi network secretory vesicles in rat hepatocytes.
J. Cell Biol
125
,
721
732
Nilsson
T.
,
Slusarewicz
P.
,
Hoe
M. H.
,
Warren
G.
(
1993
).
Kin recognition. A model for the retention of Golgi enzymes.
FEBS Lett
330
,
1
4
Nilsson
T.
,
Hoe
M. H.
,
Slusarewicz
P.
,
Rabouille
C.
,
Watson
R.
,
Hunte
F.
,
Watzele
G.
,
Berger
E. G.
,
Warren
G.
(
1994
).
Kin recognition between medial Golgi enzymes in HeLa cells.
EMBO J
13
,
562
574
Nuwayhid
N.
,
Glaser
J. H.
,
Johnson
J. C.
,
Conrad
H. E.
,
Hauser
S. C.
,
Hirschberg
C. B.
(
1986
).
Xylosylation and glucuronosylation reactions in rat liver Golgi apparatus and endoplasmic reticulum.
J. Biol. Chem
261
,
12936
12941
Oegma
T. R. Tr.
,
Kraft
E. L.
,
Jourdian
G. W.
,
van Valen
T. R.
) (
1984
).
Phosphorylation of chondroitin sulfate in proteoglycans from the swarm rat chondrosarcoma.
J. Biol. Chem
259
,
1720
1726
Okajima
T.
,
Yoshida
K.
,
Kondo
T.
,
Furukawa
K.
(
1999
).
Human homolog of Caenorhabditis elegans sqv-3 gene is galactosyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans.
J. Biol. Chem
274
,
22915
22918
Oldberg
Å.
,
Antonsson
P.
,
Moses
J.
,
Fransson
L.-Å
(
1996
).
Amino-terminal deletions in the decorin core protein leads to the biosynthesis of proteoglycans with shorter glycosaminoglycan chains.
FEBS Lett
386
,
29
32
Orellana
A.
,
Hirschberg
C. B.
,
Wei
Z.
,
Swiedler
S. J.
,
Ishihara
M.
(
1994
).
Molecular cloning and expression of a glucosaminoglycan N-acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-producing cell line.
J. Biol. Chem
269
,
2270
2276
Piller
F.
,
Hanlon
M. H.
,
Hill
R. L.
(
1983
).
Co-purification and characterization of UDP-glucose 4-epimerase and UDP-N-acetylglucosamine 4-epimerase from porcine submaxillary glands.
J. Biol. Chem
258
,
10774
10778
Poole
A. R.
(
1986
).
Proteoglycans in health and disease: structures and functions.
Biochem. J
236
,
1
14
Puglielli
L.
,
Mandon
E. C.
,
Rancour
D. M.
,
Menon
A. K.
,
Hirschberg
C. B.
(
1999
).
Identification and purification of the rat liver Golgi membrane UDP-N-acetylgalactosamine transporter.
J. Biol. Chem
274
,
4474
4479
Puglielli
L.
,
Mandon
E. C.
,
Hirschberg
C. B.
(
1999
).
Identification, purification and characterization of the rat liver Golgi membrane ATP transporter.
J. Biol. Chem
274
,
12665
12669
Quentin
E.
,
Gladen
A.
,
Roden
L.
,
Kresse
H.
(
1990
).
A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.
Proc. Nat. Acad. Sci. USA
87
,
1342
1346
Rapraeger
A.
,
Jalkanen
M.
,
Endo
E.
,
Koda
J.
,
Bernfield
M.
(
1985
).
The cell surface proteoglycan from mouse mammary epithelial cells bears chondroitin sulfate and heparan sulfate glycosaminoglycans.
J. Biol. Chem
260
,
11046
11052
Richmond
M. E.
,
DeLuca
S.
,
Silbert
J. E.
(
1973
).
Biosynthesis of chondroitin sulfate. Microsomal acceptors of sulfate, glucuronic acid and N-acetylgalactosamine.
Biochemistry
12
,
3898
3903
Rogalski
T. M.
,
Williams
B. D.
,
Mullen
G. P.
,
Moerman
D. G.
(
1993
).
Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan.
Genes Dev
7
,
1471
1484
Rohrmann
K.
,
Niemann
R.
,
Buddecke
E.
(
1985
).
Two N-acetylgalactosaminyltransferases are involved in the biosynthesis of chondroitin sulfate.
Eur. J. Biochem
148
,
463
469
Rossi
A.
,
Bonaventure
J.
,
Delezoide
A.-L.
,
Cetta
G.
,
Superti-Furga
A.
(
1996
).
Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter.
J. Biol. Chem
271
,
18456
18464
Ruoslahti
E.
(
1988
).
Structure and biology of proteoglycans.
Annu. Rev. Cell Biol
4
,
229
255
Salmivirta
M.
,
Lidholdt
K.
,
Lindahl
U.
(
1996
).
Heparan sulfate: A piece of information.
FASEB J
10
,
1270
1279
Sandvig
K.
,
Prydz
K.
,
Hansen
S. H.
,
van Deurs
B.
(
1991
).
Ricin transport in brefeldin A-treated cells: correlation between Golgi structure and toxic effect.
J. Cell Biol
115
,
971
981
Scheiffele
P.
,
Peranen
J.
,
Simons
K.
(
1995
).
N-glycans as apical sorting signals in epithelial cells.
Nature
378
,
96
98
Scheiffele
P.
,
Roth
M. G.
,
Simons
K.
(
1997
).
Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain.
EMBO J
16
,
5501
5508
Schimpf
J.
,
Sames
K.
,
Zwilling
R.
(
1999
).
Proteoglycan distribution pattern during aging in the nematode Caenorhabditis elegans: an ultrastructural histochemical study.
Histochem. J
31
,
285
292
Shworak
N. W.
,
Liu
J.
,
Petros
L. M.
,
Zhang
L.
,
Kobayashi
M.
,
Copeland
N. G.
,
Jenkins
N. A.
,
Rosenberg
R. D.
(
1999
).
Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase.
J. Biol. Chem
274
,
5170
5184
Silbert
J. E.
,
Sugumaran
G.
(
1995
).
Intracellular membranes in the synthesis, transport and metabolism of proteoglycans.
Biochim. Biophys. Acta
1241
,
371
384
Simons
K.
,
Ikonen
E.
(
1997
).
Functional rafts in cell membranes.
Nature
387
,
569
572
Spiro
R. C.
,
Freeze
H. H.
,
Sampath
D.
,
Garcia
J. A.
(
1991
).
Uncoupling of chondroitin sulfate glycosaminoglycan synthesis by brefeldin A.
J. Cell Biol
115
,
1463
1473
Spring
J.
,
Paine-Saunders
S. E.
,
Hynes
R. O.
,
Bernfield
M.
(
1994
).
Drosophila syndecan: conservation of a cell-surface heparan sulfate proteoglycan.
Proc. Nat. Acad. Sci. USA
91
,
3334
3338
Sprong
H.
,
Kruithof
B.
,
Leijendekker
R.
,
Slot
J. W.
,
van Meer
G.
,
van der Sluijs
P.
(
1998
).
UDP-Galactose: Ceramide galactosyltransferase is a class I integral membrane protein of the endoplasmic reticulum.
J. Biol. Chem
273
,
25880
25888
Stein
T.
,
Keller
R.
,
Stuhlsatz
H. W.
,
Greiling
H.
,
Ohst
E.
,
Muller
E.
,
Scharf
H. D.
(
1982
).
Structure of the linkage-region between polysaccharide chain and core protein in bovine corneal proteokeratan sulfate.
Hoppe Seylers. Z. Physiol. Chem
363
,
825
833
Stringer
S. E.
,
Mayer-Proschel
M.
,
Kalyani
A.
,
Rao
M.
,
Gallagher
J. T.
(
1999
).
Heparin is a unique marker of progenitors in the glial cell lineage.
J. Biol. Chem
274
,
25455
25460
Sueyoshi
T.
,
Kakuta
Y.
,
Pedersen
L. C.
,
Wall
F. E.
,
Pedersen
L. G.
,
Negishi
M.
(
1998
).
A role of Lys614in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase.
FEBS Lett
433
,
211
214
Sugahara
K.
,
Yamashina
I.
,
de Waard
P.
,
Van Halbeek
H.
,
Vliegenthart
J. F.
(
1988
).
Structural studies on sulfated glycopeptides from the carbohydrate-protein linkage region of chondroitin 4-sulfate proteoglycans of swarm rat chondrosarcoma. Demonstration of the structure Gal(4-O-sulfate)beta 1–3Gal beta 1–4XYL beta 1-O-Ser.
J. Biol. Chem
263
,
10168
10174
Sugahara
K.
,
Masuda
M.
,
Harada
T.
,
Yamashina
I.
,
de Waard
P.
,
Vliegenthart
J. F. G.
(
1991
).
Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin sulfate proteoglycans of whale cartilage.
Eur. J. Biochem
202
,
805
811
Sugahara
K.
,
Mizuno
N.
,
Okumura
Y.
,
Kawasaki
T.
(
1992
).
The phosphorylated and/or sulfated structure of the carbohydrate-protein-linkage region isolated from chondroitin sulfate in the hybrid proteoglycans of Engelbreth-Holm-Swarm mouse tumor.
Eur. J. Biochem
204
,
401
406
Sugahara
K.
,
Ohi
Y.
,
Harada
T.
,
de
W. P.
,
Vliegenthart
J. F.
(
1992
).
Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage. I. Six compounds containing 0 or 1 sulfate and/or phosphate residues.
J. Biol. Chem
267
,
6027
6035
Sugahara
K.
,
Yamada
S.
,
Yoshida
K.
,
de Waard
P.
,
Vliegenthart
J. F.
(
1992
).
A novel sulfated structure in the carbohydrate-protein linkage region isolated from porcine intestinal heparin.
J. Biol. Chem
267
,
1528
1533
Sugahara
K.
,
Ohkita
Y.
,
Shibata
Y.
,
Yoshida
K.
,
Ikegami
A.
(
1995
).
Structural studies on the hexasaccharide alditols isolated from the carbohydrate-protein linkage region of dermatan sulfate proteoglycans of bovine aorta. Demonstration of iduronic acid-containing components.
J. Biol. Chem
270
,
7204
7212
Sugahara
K.
,
Tsuda
H.
,
Yoshida
K.
,
Yamada
S.
,
de
B. T.
,
Vliegenthart
J. F.
(
1995
).
Structure determination of the octa-and decasaccharide sequences isolated from the carbohydrate-protein linkageregion of porcine intestinal heparin.
J. Biol. Chem
270
,
22914
22923
Sugumaran
G.
,
Katsman
M.
,
Silbert
J. E.
(
1992
).
Effects of brefeldin A on the localization of chondroitin sulfate-synthesizing enzymes. Activities in subfractions of the Golgi from chick embryo epiphyseal cartilage.
J. Biol. Chem
267
,
8802
8806
Sugumaran
G.
,
Katsman
M.
,
Sunthankar
P.
,
Drake
R. R.
(
1997
).
Biosynthesis of chondroitin sulfate. Purification of glucuronosyl transferase II and use of photoaffinity labeling for characterization of the enzyme as an 80-kDa protein.
J. Biol. Chem
272
,
14399
14403
Sugumaran
G.
,
Katsman
M.
,
Silbert
J. E.
(
1998
).
Subcellular co-localization and potential interaction of glucuronosyltransferases with nascent proteochondroitin sulphate at Golgi sites of chondroitin synthesis.
Biochem. J
329
,
203
208
Svennevig
K.
,
Prydz
K.
,
Kolset
S. O.
(
1995
).
Proteoglycans in polarized epithelial Madin-Darby canine kidney cells.
Biochem. J
311
,
881
888
Szumilo
T.
,
Zeng
Y.
,
Pastuszak
I.
,
Drake
R.
,
Szumilo
H.
,
Elbein
A. D.
(
1996
).
Purification to homogeneity and properties of UDP-GlcNAc (GalNAc) pyrophosphorylase.
J. Biol. Chem
271
,
13147
13154
Toma
L.
,
Pinhal
M. A.
,
Dietrich
C. P.
,
Nader
H. B.
,
Hirschberg
C. B.
(
1996
).
Transport of UDP-galactose into the Golgi lumen regulates the biosynthesis of proteoglycans.
J. Biol. Chem
271
,
3897
3901
Toma
L. P.
,
Berninsone
P.
,
Hirschberg
C. B.
(
1998
).
The putative heparin-specific N-acetylglucosaminyl N-deacetylase/N-sulfotransferase allso occurs in non-heparin-producing cells.
J. Biol. Chem
273
,
22458
22465
Tumova
S.
,
Hatch
B. A.
,
Law
D. J.
,
Bame
K. J.
(
1999
).
Basic fibroblast growth factor does not prevent heparan sulphate proteoglycan catabolism in intact cells, but it alters the distribution of the glycosaminoglycan degradation products.
Biochem. J
337
,
471
481
Uchimura
K.
,
Muramatsu
H.
,
Kadomatsu
K.
,
Fan
Q. W.
,
Kurosawa
N.
,
Mitsuoka
C.
,
Kannagi
R.
,
Habuchi
O.
,
Muramatsu
T.
(
1998
).
Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase.
J. Biol. Chem
273
,
22577
83
Uhlin-Hansen
L.
,
Yanagishita
M.
(
1993
).
Differential effect of brefeldin A on the biosynthesis of heparan sulfate and chondroitin/dermatan sulfate proteoglycans in rat ovarian granulosa cells in culture.
J. Biol. Chem
268
,
17370
17376
Vertel
B. M.
,
Velasco
A.
,
LaFrance
S.
,
Walters
L.
,
Kaczman-Daniel
K.
(
1989
).
Precursors of chondroitin sulfate proteoglycan are segregated within a subcompartment of the chondrocyte endoplasmic reticulum.
J. Cell Biol
109
,
1827
1836
Vertel
B. M.
,
Walters
L. M.
,
Flay
N.
,
Kearns
A. E.
,
Schwartz
N. B.
(
1993
).
Xylosylation is an endoplasmic reticulum to Golgi event.
J. Biol. Chem
268
,
11105
11112
Watanabe
N.
,
Kawashima
H.
,
Li
Y.-F.
,
Miyasaka
M.
(
1999
).
Identification and characterization of ligands for L-selectin in the kidney. III. Characterization of L-selectin reactive heparan sulfate proteoglycans.
J. Biochem
125
,
826
831
Wei
Z.
,
Swiedler
S. J.
,
Ishihara
M.
,
Orellana
A.
,
Hirschberg
C. B.
(
1993
).
A single protein catalyzes both N-deacetylation and N-sulfation during the biosynthesis of heparan sulfate.
Proc. Nat. Acad. Sci. USA
90
,
3885
3888
Werneck
C. C.
,
Oliveira-Dos-Santos
A. J.
,
Silva
L.-C. F.
,
Villa-Verde
D. M. S.
,
Savino
W.
,
Mourão
P. A. S.
(
1999
).
Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region.
J. Cell. Physiol
178
,
51
62
Wong-Palms
S.
,
Plaas
A. H.
(
1995
).
Glycosaminoglycan addition to proteoglycans by articular chondrocytes—evidence for core protein-specific pathways.
Arch. Biochem. Biophys
319
,
383
392
Yamauchi
S.
,
Hirahara
Y.
,
Usui
H.
,
Takeda
Y.
,
Hoshino
M.
,
Fukuta
M.
,
Kimura
J. H.
,
Habuchi
O.
(
1999
).
Purification andcharacterization of chondroitin 4-sulfotransferase from the culture medium of a rat chondrosarcoma cell line.
J. Biol. Chem
274
,
2456
2463
Yeaman
C.
,
Le Gall
A. H.
,
Baldwin
A. N.
,
Monlauzeur
L.
,
Le Bivic
A.
,
Rodriguez-Boulan
E.
(
1997
).
The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells.
J. Cell Biol
139
,
929
940
Zhang
L.
,
Esko
J. D.
(
1994
).
Amino acid detrminants that drive heparan sulfate assembly in a proteoglycan.
J. Biol. Chem
269
,
19295
19299
Zhang
L.
,
David
G.
,
Esko
J. D.
(
1995
).
Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans.
J. Biol. Chem
270
,
27127
27135
Zheng
X.
,
Lu
D.
,
Sadler
J. E.
(
1999
).
Apical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
J. Biol. Chem
274
,
1596
1605
Zimmermann
D.
,
Rouslahti
E.
(
1989
).
Multiple domains of the large fibroblast proteoglycan, versican.
EMBO J
8
,
2975
2981
This content is only available via PDF.