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Publication : Polysialylation controls dendritic cell trafficking by regulating chemokine recognition.

First Author  Kiermaier E Year  2016
Journal  Science Volume  351
Issue  6269 Pages  186-90
PubMed ID  26657283 Mgi Jnum  J:229318
Mgi Id  MGI:5751623 Doi  10.1126/science.aad0512
Citation  Kiermaier E, et al. (2016) Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science 351(6269):186-90
abstractText  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.
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