Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc

Yakubenia, Sviatlana; Frommhold, David; Schölch, Dirk; Hellbusch, Christina C.; Körner, Christian; Petri, Bjӧrn; Jones, Claire; Ipe, Ute; Bixel, M. Gabriele; Krempien, Robert; Sperandio, Markus; Wild, Martin K.

doi:10.1182/blood-2008-01-132035

Cited by 39 publications

(25 citation statements)

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“…Thus, mice homozygous for a Slc35c1-null mutation show hypofucosylation of glycoproteins, the absence of selectin ligands, growth retardation, and postnatal defects in various organs (18,43). However, these defects are significantly less severe than those associated with the mutation of FX, which encodes an enzyme that converts GDP-mannose to GDP-fucose, although some of the defects overlap (44).…”

Section: Discussionmentioning

confidence: 99%

Two Pathways for Importing GDP-fucose into the Endoplasmic Reticulum Lumen Function Redundantly in the O-Fucosylation of Notch in Drosophila

Ishikawa

Ayukawa

Nakayama

et al. 2010

Journal of Biological Chemistry

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Notch is a transmembrane receptor that shares homology with proteins containing epidermal growth factor-like repeats and mediates the cell-cell interactions necessary for many cell fate decisions. In Drosophila, O-fucosyltransferase 1 catalyzes the O-fucosylation of these epidermal growth factor-like repeats. This O-fucose elongates, resulting in an O-linked tetrasaccharide that regulates the signaling activities of Notch. Fucosyltransferases utilize GDP-fucose, which is synthesized in the cytosol, but fucosylation occurs in the lumen of the endoplasmic reticulum (ER) and Golgi. Therefore, GDP-fucose uptake into the ER and Golgi is essential for fucosylation. However, although GDP-fucose biosynthesis is well understood, the mechanisms and intracellular routes of GDP-fucose transportation remain unclear. Our previous study on the Drosophila Golgi GDP-fucose transporter (Gfr), which specifically localizes to the Golgi, suggested that another GDP-fucose transporter(s) exists in Drosophila. Here, we identified Efr (ER GDP-fucose transporter), a GDP-fucose transporter that localizes specifically to the ER. Efr is a multifunctional nucleotide sugar transporter involved in the biosynthesis of heparan sulfate-glycosaminoglycan chains and the O-fucosylation of Notch. Comparison of the fucosylation defects in the N-glycans in Gfr and Efr mutants revealed that Gfr and Efr made distinct contributions to this modification; Gfr but not Efr was crucial for the fucosylation of N-glycans. We also found that Gfr and Efr function redundantly in the O-fucosylation of Notch, although they had different localizations and nucleotide sugar transportation specificities. These results indicate that two pathways for the nucleotide sugar supply, involving two nucleotide sugar transporters with distinct characteristics and distributions, contribute to the O-fucosylation of Notch.

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Section: Discussionmentioning

confidence: 99%

Two Pathways for Importing GDP-fucose into the Endoplasmic Reticulum Lumen Function Redundantly in the O-Fucosylation of Notch in Drosophila

Ishikawa

Ayukawa

Nakayama

et al. 2010

Journal of Biological Chemistry

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“…4,[28][29][30] Therefore, we compared WBC counts in St3gal4-and St3gal6-deficient mice both individually and combined. WBC counts in St3gal4 or St3gal6 single-deficient mice were unaltered from normal ( Figure 2A).…”

Section: St3gal-vi and St3gal-iv Deficiency In Hemostasismentioning

confidence: 99%

Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands

Yang

Nußbaum

Grewal

et al. 2012

Blood

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AbstractBinding of selectins to their glycan ligands is a prerequisite for successful leukocyte trafficking. During synthesis and transport through the secretory pathway, selectin ligands are constructed with the participation of one or more sialyltransferases of the ST3Gal subfamily. Previous studies established that ST3Gal-IV only partially contributes to selectin ligand formation, indicating that other ST3Gal-sialyltransferases are involved. By generating and analyzing St3gal6-null mice and St3gal4/St3gal6 double-deficient mice, in the present study, we found that binding of E- and P-selectin to neutrophils and L-selectin binding to lymph node high endothelial venules is reduced in the absence of ST3Gal-VI and to a greater extent in double-deficient mice. In an ex vivo flow chamber assay, P- and E-selectin–dependent leukocyte rolling was mildly reduced in St3gal6-null mice and more severely in double-deficient mice. In inflamed cremaster muscle venules of St3gal6-null mice, we found impaired P-selectin–dependent, but not E-selectin–dependent leukocyte rolling, whereas in double-deficient mice, E-selectin–dependent rolling was almost completely absent. Furthermore, neutrophil recruitment into the inflamed peritoneal cavity and lymphocyte homing to secondary lymphoid organs were impaired in St3gal6-null mice and more severely in double-deficient mice. The results of the present study demonstrate the coordinated participation of both ST3Gal-VI and ST3Gal-IV in the synthesis of functional selectin ligands.

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“…The generation of bone marrow chimeric mice was conducted as described. 19 The animal experiments were approved by the Regierungspräsidium Karlsruhe, Germany (AZ .81/G-67/03, AZ .81/G-08/08) and the Regierung Oberbayern, Germany (AZ 55.2-1-54-2531-80-07 and -134/08).…”

Section: Introductionmentioning

confidence: 99%

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

Frommhold

Kamphues

Hepper

et al. 2010

Blood

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133

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The receptor for advanced glycation end products (RAGE) contributes to the inflammatory response in many acute and chronic diseases. In this context, RAGE has been identified as a ligand for the ␤ 2 -integrin Mac-1 under static in vitro conditions. Because intercellular adhesion molecule (ICAM)-1 also binds ␤ 2 -integrins, we studied RAGE ؊/؊ , Icam1 ؊/؊ , and RAGE ؊/؊ Icam1 ؊/؊ mice to define the relative contribution of each ligand for leukocyte adhesion in vivo. We show that trauma-induced leukocyte adhesion in cremaster muscle venules is strongly dependent on RAGE and ICAM-1 acting together in an overlapping fashion. Additional in vivo experiments in chimeric mice lacking endothelium-expressed RAGE and ICAM-1 located the adhesion defect to the endothelial compartment. Using microflow chambers coated with P-selectin, CXCL1, and soluble RAGE (sRAGE) demonstrated that sRAGE supports leukocyte adhesion under flow conditions in a Mac-1-but not LFA-1-dependent fashion. A static adhesion assay revealed that wild-type and RAGE ؊/؊ neutrophil adhesion and spreading were similar on immobilized sRAGE or fibrinogen. These observations indicate a crucial role of endotheliumexpressed RAGE as Mac-1 ligand and uncover RAGE and ICAM-1 as a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute traumainduced inflammatory response in vivo. IntroductionLeukocyte recruitment into inflamed tissue follows a well-defined cascade of events, beginning with the capture of free-flowing leukocytes to the vessel wall and subsequent leukocyte rolling along and adhesion to the inflamed endothelial layer. 1,2 During rolling, leukocytes get into close contact with the endothelial surface, which allows endothelial bound chemokines to interact with their specific receptors on the leukocyte surface. This triggers the activation of integrins, which leads to firm leukocyte arrest on the endothelium. In addition, integrindependent signaling events induce cytoskeletal rearrangements and cell polarization, modifications necessary in helping to prepare the attached leukocyte to spread and crawl in search for its way out of the vasculature into tissue. [2][3][4][5][6] Recent evidence has shown that the ␤ 2 -integrin Mac-1 is crucially involved in transducing Syk-dependent signaling events necessary for sustained leukocyte adhesion. [7][8][9] The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that has been identified to be a major player in chronic inflammatory conditions. 10,11 This has been mainly attributed to its strong effects on perpetuating nuclear factor-B (NF-B) activation and NF-Bdependent signaling 10,11 and its ability to induce its own expression. 10,12 Besides its function as a signaling molecule, RAGE also binds to Mac-1, which has been demonstrated under in vitro conditions. 13 In addition, a reduction of leukocyte extravasation into the inflamed peritoneal cavity was found in RAGE Ϫ/Ϫ mice after intraperitoneal application of th...

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Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc

Cited by 39 publications

References 60 publications

Two Pathways for Importing GDP-fucose into the Endoplasmic Reticulum Lumen Function Redundantly in the O-Fucosylation of Notch in Drosophila

Two Pathways for Importing GDP-fucose into the Endoplasmic Reticulum Lumen Function Redundantly in the O-Fucosylation of Notch in Drosophila

Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

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