Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

E. Kiermaier, C. Moussion, C. Veldkamp, R. Gerardy  Schahn, I. De Vries, L. Williams, G. Chaffee, A. Phillips, F. Freiberger, R. Imre, D. Taleski, R. Payne, A. Braun, R. Förster, K. Mechtler, M. Mühlenhoff, B. Volkman, M.K. Sixt, Science 351 (2016) 186–190.

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Journal Article | Published | English
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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.
Publishing Year
Date Published
2016-01-08
Journal Title
Science
Acknowledgement
We thank S. Schüchner and E. Ogris for kindly providing the antibody to GFP, M. Helmbrecht and A. Huber for providing Nrp2−/− mice, the IST Scientific Support Facilities for excellent services, and J. Renkawitz and K. Vaahtomeri for critically reading the manuscript.
Volume
351
Issue
6269
Page
186 - 190
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Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 2016;351(6269):186-190. doi:10.1126/science.aad0512
Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy  Schahn, R., De Vries, I., Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science, 351(6269), 186–190. https://doi.org/10.1126/science.aad0512
Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy  Schahn, Ingrid De Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science 351, no. 6269 (2016): 186–90. https://doi.org/10.1126/science.aad0512.
E. Kiermaier et al., “Polysialylation controls dendritic cell trafficking by regulating chemokine recognition,” Science, vol. 351, no. 6269, pp. 186–190, 2016.
Kiermaier E, Moussion C, Veldkamp C, Gerardy  Schahn R, De Vries I, Williams L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269), 186–190.
Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science, vol. 351, no. 6269, American Association for the Advancement of Science, 2016, pp. 186–90, doi:10.1126/science.aad0512.

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