Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21 Journal Article


Authors: Rey-Gallardo, A.; Escribano, C.; Delgado-Martín, C.; Rodriguez-Fernández, J. L.; Gerardy-Schahn, R.; Rutishauser, U.; Corbi, A. L.; Vega, M. A.
Article Title: Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21
Abstract: Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here, we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19. We have also explored the molecular mechanisms underlying the selective enhancing effect of PSA on CCL21-driven chemotaxis of DCs. In this regard, we found out that prevention of DC polysialylation decreased CCL21 activation of JNK and Akt signaling pathways, both associated with CCR7-mediated chemotaxis. We also report that the enhanced PSA-mediated effect on DC migration towards CCL21 relied on the highly basic C-terminal region of this chemokine and depended on the PSA acceptor molecule neuropilin-2 (NRP2) and on the polysialyltransferase ST8SiaIV. Altogether, our data indicate that the CCR7/CCL21/NRP2/ST8SiaIV functional axis constitutes an important guidance clue for DC targeting to lymphoid organs. © 2010 The Author.
Keywords: signal transduction; protein kinase b; human cell; animals; cells, cultured; models, biological; dendritic cell; stress activated protein kinase; carboxy terminal sequence; rna, small interfering; enzyme activation; cell strain cos7; cercopithecus aethiops; cos cells; dendritic cells; amino acid sequence; molecular sequence data; protein processing, post-translational; sequence homology, amino acid; chemotaxis; polysialic acid; cell migration; cell movement; up-regulation; chemokine receptor ccr7; site directed mutagenesis; protein interaction domains and motifs; sialic acids; ccl21; neuropilin-2; st8siaiv; neuropilin 2; secondary lymphoid tissue chemokine; sialylation; amino acids, basic; chemokine ccl21
Journal Title: Glycobiology
Volume: 20
Issue: 9
ISSN: 0959-6658
Publisher: Oxford University Press  
Date Published: 2010-09-01
Start Page: 1139
End Page: 1146
Language: English
DOI: 10.1093/glycob/cwq078
PUBMED: 20488940
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: GLYCE" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors