Publication Date:
2015-12-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiermaier, Eva -- Moussion, Christine -- Veldkamp, Christopher T -- Gerardy-Schahn, Rita -- de Vries, Ingrid -- Williams, Larry G -- Chaffee, Gary R -- Phillips, Andrew J -- Freiberger, Friedrich -- Imre, Richard -- Taleski, Deni -- Payne, Richard J -- Braun, Asolina -- Forster, Reinhold -- Mechtler, Karl -- Muhlenhoff, Martina -- Volkman, Brian F -- Sixt, Michael -- 1R15CA159202-01/CA/NCI NIH HHS/ -- R01AI058072/AI/NIAID NIH HHS/ -- R01GM09738/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):186-90. doi: 10.1126/science.aad0512. Epub 2015 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria. ; Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA. Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. ; Institute for Cellular Chemistry, Hannover Medical School [Medizinische Hochschule Hannover (MHH)], Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. ; Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA. ; Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr Gasse 7, 1030 Vienna, Austria. ; School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia. ; Institute of Immunology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. ; Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26657283" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bone Marrow Cells/physiology
;
Chemokine CCL21/*metabolism
;
*Chemotaxis
;
Dendritic Cells/*physiology
;
Glycosylation
;
Ligands
;
Lymph Nodes/cytology/*physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Mutant Strains
;
*Protein Processing, Post-Translational
;
Receptors, CCR7/*metabolism
;
Sialic Acids/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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