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Science. 2016 Jan 8;351(6269):186-90. doi: 10.1126/science.aad0512. Epub 2015 Dec 10.

Polysialylation controls dendritic cell trafficking by regulating chemokine recognition.

Author information

1
Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
2
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.
3
Institute for Cellular Chemistry, Hannover Medical School [Medizinische Hochschule Hannover (MHH)], Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
4
Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
5
Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr Gasse 7, 1030 Vienna, Austria.
6
School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
7
Institute of Immunology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
8
Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

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.

PMID:
26657283
PMCID:
PMC5583642
DOI:
10.1126/science.aad0512
[Indexed for MEDLINE]
Free PMC Article

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