Synthesis of heparan sulfate with cyclophilin B-binding properties is determined by cell type-specific expression of sulfotransferases
| Autor: | Toin H. van Kuppevelt, Audrey Deligny, Adeline Marcant, Fabrice Allain, Aurélie Melchior, Agnès Denys, Joël Mazurier |
|---|---|
| Přispěvatelé: | Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
MESH: Heparin
T-Lymphocytes Glycobiology and Extracellular Matrices Plasma protein binding MESH: Monocytes Biochemistry Monocytes MESH: Down-Regulation Substrate Specificity chemistry.chemical_compound Cyclophilins RNA interference MESH: Animals MESH: Nitrogen Cyclophilin MESH: Organ Specificity Regulation of gene expression 0303 health sciences Sulfates MESH: Gene Expression Regulation Enzymologic 030302 biochemistry & molecular biology Heparan sulfate Isoenzymes MESH: Cattle Organ Specificity MESH: Isoenzymes RNA Interference Sulfotransferases Protein Binding Gene isoform MESH: Cell Line Tumor Nitrogen MESH: RNA Interference Down-Regulation Biology Isozyme Gene Expression Regulation Enzymologic MESH: Cyclophilins 03 medical and health sciences MESH: Heparitin Sulfate Cell Line Tumor Animals Humans MESH: Protein Binding [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology 030304 developmental biology MESH: Humans Heparin Macrophages MESH: Macrophages Cell Biology Tissue engineering and pathology [NCMLS 3] MESH: Sulfotransferases MESH: T-Lymphocytes chemistry Cell culture Cattle MESH: Substrate Specificity Heparitin Sulfate MESH: Sulfates |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (3), pp.1701-15. ⟨10.1074/jbc.M109.018184⟩ Journal of Biological Chemistry, 285, 3, pp. 1701-15 Journal of Biological Chemistry, 2010, 285 (3), pp.1701-15. ⟨10.1074/jbc.M109.018184⟩ Journal of Biological Chemistry, 285, 1701-15 |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M109.018184⟩ |
| Popis: | Contains fulltext : 89091.pdf (Publisher’s version ) (Open Access) Cyclophilin B (CyPB) induces migration and adhesion of T lymphocytes via a mechanism that requires interaction with 3-O-sulfated heparan sulfate (HS). HS biosynthesis is a complex process with many sulfotransferases involved. N-Deacetylases/N-sulfotransferases are responsible for N-sulfation, which is essential for subsequent modification steps, whereas 3-O-sulfotransferases (3-OSTs) catalyze the least abundant modification. These enzymes are represented by several isoforms, which differ in term of distribution pattern, suggesting their involvement in making tissue-specific HS. To elucidate how the specificity of CyPB binding is determined, we explored the relationships between the expression of these sulfotransferases and the generation of HS motifs with CyPB-binding properties. We demonstrated that high N-sulfate density and the presence of 2-O- and 3-O-sulfates determine binding of CyPB, as evidenced by competitive experiments with heparin derivatives, soluble HS, and anti-HS antibodies. We then showed that target cells, i.e. CD4+ lymphocyte subsets, monocytes/macrophages, and related cell lines, specifically expressed high levels of NDST2 and 3-OST3 isoforms. Silencing the expression of NDST1, NDST2, 2-OST, and 3-OST3 by RNA interference efficiently decreased binding and activity of CyPB, thus confirming their involvement in the biosynthesis of binding sequences for CyPB. Moreover, we demonstrated that NDST1 was able to partially sulfate exogenous substrate in the absence of NDST2 but not vice versa, suggesting that both isoenzymes do not have redundant activities but do have rather complementary activities in making N-sulfated sequences with CyPB-binding properties. Altogether, these results suggest a regulatory mechanism in which cell type-specific expression of certain HS sulfotransferases determines the specific binding of CyPB to target cells. |
| Databáze: | OpenAIRE |
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