Golgi Localization of Carbohydrate Sulfotransferases Is a Determinant of L-selectin Ligand Biosynthesis

Graffenried, Christopher L. de; Bertozzi, Carolyn R.

doi:10.1074/jbc.m304928200

Cited by 32 publications

(29 citation statements)

References 88 publications

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“…Consequently, we propose that a portion of the L-selectin ligand remaining in GlcNAc6ST-2 null mice is on core 2 glycans, the sulfation of which is mediated by GlcNAc6ST-1. Consistent with the possibility, de Graffenried and Bertozzi (28) found that GlcNAc6ST-1 preferably modifies the capping group on the core 2 branch rather than that on core 1-extended glycans. Furthermore, Hiraoka et al (47) observed that mice deficient in both GlcNAc6ST-2 and C2GlcNAcT exhibit a greater reduction in lymphocyte homing than GlcNAc6ST-2 single knockout mice.…”

Section: Altered Expression Pattern Of Meca-79 Epitope In Hev Ofsupporting

confidence: 60%

“…CD34, GlyCAM-1, and MAd-CAM-1) (17,(25)(26)(27). Transfection with cDNA encoding either of the two GlcNAc6STs (GlcNAc6ST-1 and GlcNAc6ST-2) contribute to the formation of sialyl 6-sulfo Lewis X and the MECA-79 epitope on the transfectants (17,25,26,28). We further characterized their substrate specificities and enzymological prop-erties employing protein A-fused GlcNAc6ST-1 and GlcNAc6ST-2 proteins.…”

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confidence: 99%

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N-Acetylglucosamine 6-O-Sulfotransferase-1 Regulates Expression of L-Selectin Ligands and Lymphocyte Homing

Uchimura

Kadomatsu

El-Fasakhany

et al. 2004

Journal of Biological Chemistry

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Lymphocyte homing is initiated by the binding of Lselectin on lymphocytes to its ligands on high endothelial venules (HEV). Sialyl 6-sulfo Lewis X is a major capping group of L-selectin ligands. N-Acetylglucosamine (GlcNAc) 6-sulfation is essential for the ligand activity, and is catalyzed by GlcNAc 6-O-sulfotransferases (GlcNAc6STs) of which GlcNAc6ST-1 and GlcNAc6ST-2 are expressed in HEV. Here, we report that mice deficient in GlcNAc6ST-1 were impaired in the elaboration of sialyl 6-sulfo Lewis X in HEV and that an epitope of L-selectin ligands recognized by the MECA-79 antibody was greatly reduced or abolished in the abluminal aspect of HEV. Lymphocyte homing to peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches was significantly reduced in GlcNAc6ST-1 null mice. These results demonstrate that GlcNAc6ST-1 is involved in lymphocyte homing in vivo, and indicate that GlcNAc6ST-1 and -2 play complementary roles. The importance of GlcNAc6ST-1 is particularly highlighted by its involvement in lymphocyte homing to Peyer's patches where GlcNAc6ST-2 expression is undetectable.

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Section: Altered Expression Pattern Of Meca-79 Epitope In Hev Ofsupporting

confidence: 60%

mentioning

confidence: 99%

N-Acetylglucosamine 6-O-Sulfotransferase-1 Regulates Expression of L-Selectin Ligands and Lymphocyte Homing

Uchimura

Kadomatsu

El-Fasakhany

et al. 2004

Journal of Biological Chemistry

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“…Carbohydrate sulfation has been shown to be important for the formation of ligands that bind adhesion molecules belonging to the selectin family (4,5). Studies that examine the ability of sulfated carbohydrates to inhibit selectin-ligand recognition also highlight the importance of sulfation to human health.…”

Section: (Gal␤13)galnac␣-o-bn and Gal␤13galnac␣-o-al (Where Al Is mentioning

confidence: 99%

Identification of Physiologically Relevant Substrates for Cloned Gal: 3-O-Sulfotransferases (Gal3STs)

Chandrasekaran¹,

Lakhaman

Chawda³

et al. 2004

Journal of Biological Chemistry

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Sulfated glycoconjugates regulate biological processes such as cell adhesion and cancer metastasis. We examined the acceptor specificities and kinetic properties of three cloned Gal:3-O-sulfotransferases (Gal3STs) ST-2, ST-3, and ST-4 along with a purified Gal3ST from colon carcinoma LS180 cells. Gal3ST-2 was the dominant Gal3ST in LS180. While the mucin core-2 structure Gal␤1,4GlcNAc␤1,6(3-O-MeGal␤1,3)GalNAc␣-O-Bn (where Bn is benzyl) and the disaccharide Gal␤1,4GlcNAc served as high affinity acceptors for Gal3ST-2 and Gal3ST-3, 3-O-MeGal␤1,4GlcNAc␤1,-6(Gal␤1,3)GalNAc␣-O-Bn and Gal␤1,3GalNAc␣-O-Al (where Al is allyl) were efficient acceptors for Gal3ST-4. The activities of Gal3ST-2 and Gal3ST-3 could be distinguished with the Globo H precursor (Gal␤1,3GalNAc␤1,3Gal␣-O-Me) and fetuin triantennary asialoglycopeptide. Gal3ST-2 acted efficiently on the former, while Gal3ST-3 showed preference for the latter. Gal3ST-4 also acted on the Globo H precursor but not the glycopeptide. In support of the specificity, Gal3ST-2 activity toward the Gal␤1,4GlcNAc␤ unit on mucin core-2 as well as the Globo H precursor could be inhibited competitively by Gal␤1,4GlcNAc␤1,6(3-OsulfoGal␤1,3)GalNAc␣-O-Bn but not 3-O-sulfoGal␤1,-4GlcNAc␤1,6(Gal␤1,3)GalNAc␣-O-Bn. Remarkably these sulfotransferases were uniquely specific for sulfated substrates: Gal3ST-3 utilized Gal␤1,4(6-O-sulfo)-GlcNAc␤-O-Al as acceptor, Gal3ST-2 acted efficiently on Gal␤1,3(6-O-sulfo)GlcNAc␤-O-Al, and Gal3ST-4 acted efficiently on Gal␤1,3(6-O-sulfo)GalNAc␣-O-Al. Mg 2؉ , Mn 2؉ , and Ca 2؉ stimulated the activities of Gal3ST-2, whereas only Mg 2؉ augmented Gal3ST-3 activity. Divalent cations did not stimulate Gal3ST-4, although inhibition was noted at high Mn 2؉ concentrations. The fine substrate specificities of Gal3STs indicate a distinct physiological role for each enzyme.

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“…Considering the previous finding that both of these sulfotransferases can transfer sulfate onto core 2-branched O-glycans, and our observation that sulfate residues were exclusively present on core 2 branched oligosaccharides of the colonic mucins, the preference for a particular acceptor oligosaccharide structure may not account for the differential activity of GlcNAc6ST-1 and GlcNAc6ST-2 for the colonic mucins. One possible explanation is that the subcellular distribution of GlcNAc6ST-2 is more suitable for transferring sulfate to the GlcNAc-terminated O-glycans of colonic mucins, because GlcNAc6ST-1 is confined to the trans-Golgi network, whereas GlcNAc6ST-2 is distributed throughout the Golgi apparatus (30). Another possibility is that differential preferences of GlcNAc6ST-1 and GlcNAc6ST-2 for the Muc2 core protein, a major colonic mucin, accounts for the difference.…”

Section: Discussionmentioning

confidence: 95%

Two Roles of Mucin Sulfation

Kawashima¹

2010

TIGG

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Recent studies using gene-targeted mice have revealed various physiological functions of sulfated glycans. Studies using gene-targeted mice deficient in two sulfotransferases, N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2, showed that these sulfotransferases catalyze sulfation of mucin-like glycoproteins expressed on high endothelial venules (HEVs) in lymph nodes, and play critical roles in lymphocyte homing and immune surveillance. More recent studies using GlcNAc6ST-2-deficeint mice revealed that GlcNAc6ST-2 is expressed not only in lymph node HEVs but also in the colonic epithelial cells in mice, and has protective function in experimental colitis in mice by catalyzing sulfation of the colonic mucins. In this review, the two distinct functions of sulfation of mucins or mucin-like glycoproteins by sulfotransferases in lymph nodes and colon will be discussed.

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Golgi Localization of Carbohydrate Sulfotransferases Is a Determinant of L-selectin Ligand Biosynthesis

Cited by 32 publications

References 88 publications

N-Acetylglucosamine 6-O-Sulfotransferase-1 Regulates Expression of L-Selectin Ligands and Lymphocyte Homing

N-Acetylglucosamine 6-O-Sulfotransferase-1 Regulates Expression of L-Selectin Ligands and Lymphocyte Homing

Identification of Physiologically Relevant Substrates for Cloned Gal: 3-O-Sulfotransferases (Gal3STs)

Two Roles of Mucin Sulfation

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