Polysialylation controls dendritic cell trafficking by regulating chemokine recognition
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.
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Author
Kiermaier, EvaISTA 
;
Moussion, ChristineISTA;
Veldkamp, Christopher;
Gerardy Schahn, Rita;
de Vries, IngridISTA;
Williams, Larry;
Chaffee, Gary;
Phillips, Andrew;
Freiberger, Friedrich;
Imre, Richard;
Taleski, Deni;
Payne, Richard
All
;
Moussion, ChristineISTA;
Veldkamp, Christopher;
Gerardy Schahn, Rita;
de Vries, IngridISTA;
Williams, Larry;
Chaffee, Gary;
Phillips, Andrew;
Freiberger, Friedrich;
Imre, Richard;
Taleski, Deni;
Payne, Richard
All
Corresponding author has ISTA affiliation
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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
Publisher
American Association for the Advancement of 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.
Acknowledged SSUs
Volume
351
Issue
6269
Page
186 - 190
IST-REx-ID
Cite this
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. American Association for the Advancement of Science. 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. American Association for the Advancement of Science, 2016. 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. American Association for the Advancement of Science, 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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