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Polysialylated neuropilin-2 is expressed on the surface of human dendritic cells and modulates dendritic cell-T lymphocyte interactions.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Oct 19; Vol. 282 (42), pp. 30346-56. Date of Electronic Publication: 2007 Aug 15. - Publication Year :
- 2007
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Abstract
- Polysialic acid (PSA) is a unique linear homopolymer of alpha2,8-linked sialic acid that has been identified as a posttranslational modification on only five mammalian proteins. Studied predominantly on neural cell adhesion molecule (NCAM) during development of the vertebrate nervous system, PSA modulates cell interactions mediated by NCAM and other adhesion molecules. An isoform of NCAM (CD56) on natural killer (NK) cells is the only protein known to be polysialylated in cells of the immune system, yet the function of PSA in NK cells remains unclear. We show here that neuropilin-2 (NRP-2), a receptor for the semaphorin and vascular endothelial growth factor families in neurons and endothelial cells, respectively, is expressed on the surface of human dendritic cells and is polysialylated. Expression of NRP-2 is up-regulated during dendritic cell maturation, coincident with increased expression of ST8Sia IV, one of the key enzymes of PSA biosynthesis, and with the appearance of PSA on the cell surface. PSA on NRP-2 is resistant to digestion with peptide N-glycosidase F but is sensitive to release under alkaline conditions, suggesting that PSA chains are added to O-linked glycans of NRP-2. Removal of polysialic acid from the surface of dendritic cells or binding of NRP-2 with specific IgG promoted dendritic cell-induced activation and proliferation of T lymphocytes. Thus, this newly recognized polysialylated protein on the surface of dendritic cells influences dendritic cell-T lymphocyte interactions through one or more of its distinct extracellular domains.
- Subjects :
- Antibodies immunology
Antibodies pharmacology
Cell Communication drug effects
Cell Line
Cell Proliferation drug effects
Dendritic Cells cytology
Dendritic Cells immunology
Endothelial Cells cytology
Endothelial Cells immunology
Endothelial Cells metabolism
Humans
Killer Cells, Natural cytology
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Lymphocyte Activation drug effects
Lymphocyte Activation physiology
Neural Cell Adhesion Molecules immunology
Neural Cell Adhesion Molecules metabolism
Neurons cytology
Neurons immunology
Neuropilin-2 immunology
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase chemistry
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase pharmacology
Protein Isoforms immunology
Protein Isoforms metabolism
Protein Processing, Post-Translational drug effects
Sialic Acids immunology
Sialyltransferases immunology
Sialyltransferases metabolism
T-Lymphocytes cytology
T-Lymphocytes immunology
Up-Regulation drug effects
Up-Regulation physiology
Cell Communication physiology
Dendritic Cells metabolism
Neuropilin-2 metabolism
Protein Processing, Post-Translational physiology
Sialic Acids metabolism
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 42
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17699524
- Full Text :
- https://doi.org/10.1074/jbc.M702965200