title: Polysialylation controls dendritic cell trafficking by regulating chemokine recognition.
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.
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Kiermaier
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Moussion
authors.affiliation: 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.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Veldkamp
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School [Medizinische Hochschule Hannover (MHH)], Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: de Vries
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Larry G
authors.initials: LG
authors.lastname: Williams
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Chaffee
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Phillips
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School [Medizinische Hochschule Hannover (MHH)], Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Freiberger
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr Gasse 7, 1030 Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Imre
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Deni
authors.initials: D
authors.lastname: Taleski
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Payne
authors.affiliation: Institute of Immunology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Asolina
authors.initials: A
authors.lastname: Braun
authors.affiliation: Institute of Immunology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr Gasse 7, 1030 Vienna, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.affiliation: Institute for Cellular Chemistry, Hannover Medical School [Medizinische Hochschule Hannover (MHH)], Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Volkman
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D054421:Chemokine CCL21 / Q000378:metabolism*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000502:physiology*; D006031:Glycosylation; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011499:Protein Processing, Post-Translational; D054400:Receptors, CCR7 / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D008024:Ligands; D054400:Receptors, CCR7; D012794:Sialic Acids; C021319:polysialic acid