Work

Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Year: 2015

Type: article

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.

Source: Science

DOI: 10.1126/science.aad0512

Authors: Eva Kiermaier, Christine Moussion, Christopher T. Veldkamp, Rita Gerardy-Schahn, Ingrid de Vries, Larry G. Williams, Gary R. Chaffee, Andrew J. Phillips, Friedrich Freiberger, Richard Imre, Deni Taleski, Richard J. Payne, Asolina Braun, Reinhold Förster, Karl Mechtler, Martina Mühlenhoff, Brian F. Volkman, Michael Sixt

Institutions: Institute of Science and Technology Austria, University of Wisconsin–Whitewater, Medical College of Wisconsin, Medizinische Hochschule Hannover, Research Institute of Molecular Pathology, Vienna Biocenter, The University of Sydney

Language: English

Topic: Glycosylation and Glycoproteins Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Austrian Science Fund, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, H2020 European Research Council

Awards: Structural Basis for Chemokine Function, Sulfotyrosine-guided discovery of small molecule chemokine inhibitors, Self-Learning Search Algorithms for High-Res Mass Spectra, G4387754249, ATTENUATION CONTROL OF GENE EXPRESSION IN BACTERIA, G4977696269, G6238082157, Structural studies of chemokines that target metastatic cancer cells to the lymph, G9000211789, Structural Basis for Chemokine Function

OpenAlex ID: W2273967916

FWCI: 7.522

Cites: 35

Cited by: 162

Related to: 10