Medical College of Wisconsin
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Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science 2016 Jan 08;351(6269):186-90

Date

12/15/2015

Pubmed ID

26657283

Pubmed Central ID

PMC5583642

DOI

10.1126/science.aad0512

Scopus ID

2-s2.0-84955091858   62 Citations

Abstract

The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.

Author List

Kiermaier E, Moussion C, Veldkamp CT, Gerardy-Schahn R, de Vries I, Williams LG, Chaffee GR, Phillips AJ, Freiberger F, Imre R, Taleski D, Payne RJ, Braun A, F├Ârster R, Mechtler K, M├╝hlenhoff M, Volkman BF, Sixt M

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow Cells
Chemokine CCL21
Chemotaxis
Dendritic Cells
Glycosylation
Ligands
Lymph Nodes
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Protein Processing, Post-Translational
Receptors, CCR7
Sialic Acids
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46