title: The sweet spot: how GAGs help chemokines guide migrating cells.
abstract: Glycosaminoglycans are polysaccharides that occur both at the cell surface and within extracellular matrices. Through their ability to bind to a large array of proteins, almost 500 of which have been identified to date, including most chemokines, these molecules regulate key biologic processes at the cell-tissue interface. To do so, glycosaminoglycans can provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and can also directly contribute to biologic activities or signaling processes. The binding of chemokines to glycosaminoglycans, which, at the biochemical level, has been mostly studied using heparin, has traditionally been thought of as a mechanism for maintaining haptotactic gradients within tissues along which cells can migrate directionally. Many aspects of chemokine-glycosaminoglycan interactions, however, also suggest that the formation of these complexes could serve additional purposes that go well beyond a simple immobilization process. In addition, progress in glycobiology has revealed that glycosaminoglycan structures, in term of length, sulfation, and epimerization pattern, are specific for cell, tissue, and developmental stage. Glycosaminoglycan regulation and glycosaminoglycan diversity, which cannot be replicated using heparin, thus suggests that these molecules may fine-tune the immune response by selectively recruiting specific chemokines to cell surfaces. In this context, the aim of the present text is to review the chemokine-glycosaminoglycan complexes described to date and provide a critical analysis of the tools, molecules, and strategies that can be used to structurally and functionally investigate the formation of these complexes.
authors.affiliation: Université Grenoble Alpes, Institut de Biologie Structurale, UMR 5075, Grenoble, France; Centre National de la Recherche Scientifique, Institut de Biologie Structurale, UMR 5075, Grenoble, France; and Commissariat à l'Énergie Atomique et aux Énergies Alternatives-Direction des Sciences du Vivant, Institut de Biologie Structurale, UMR 5075, Grenoble, France; and.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Monneau
authors.affiliation: Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.affiliation: Université Grenoble Alpes, Institut de Biologie Structurale, UMR 5075, Grenoble, France; Centre National de la Recherche Scientifique, Institut de Biologie Structurale, UMR 5075, Grenoble, France; and Commissariat à l'Énergie Atomique et aux Énergies Alternatives-Direction des Sciences du Vivant, Institut de Biologie Structurale, UMR 5075, Grenoble, France; and hugues.lortat-jacob@ibs.fr.
authors.forename: Hugues
authors.initials: H
authors.lastname: Lortat-Jacob
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015398:Signal Transduction
chemical_list: D018925:Chemokines; D006025:Glycosaminoglycans; D008024:Ligands
keywords: chemokine receptor; heparan sulfate; structure–function relationships