Polysialylated neuropilin-2 is expressed on the surface of human dendritic cells and modulates dendritic cell-T lymphocyte interactions.
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.
Curreli
Sabrina
S
Institute of Human Virology, University of Maryland, Baltimore, Maryland 21201, USA.
Arany
Zita
Z
Gerardy-Schahn
Rita
R
Mann
Dean
D
Stamatos
Nicholas M
NM
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000276:immunology; D039943:Neuropilin-2 / Q000276:immunology / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000737:chemistry / Q000494:pharmacology; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D012794:Sialic Acids / Q000276:immunology / Q000378:metabolism*; D012799:Sialyltransferases / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D019006:Neural Cell Adhesion Molecules; D039943:Neuropilin-2; D020033:Protein Isoforms; D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases; C515117:ST8SIA4 protein, human; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase