Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • Chemokine CCL21 / metabolism*
  • Chemotaxis*
  • Dendritic Cells / physiology*
  • Glycosylation
  • Ligands
  • Lymph Nodes / cytology
  • Lymph Nodes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Protein Processing, Post-Translational*
  • Receptors, CCR7 / metabolism*
  • Sialic Acids / metabolism*

Substances

  • Ccr7 protein, mouse
  • Chemokine CCL21
  • Ligands
  • Receptors, CCR7
  • Sialic Acids
  • polysialic acid