Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Eva Kiermaier; Christine Moussion; Christopher T. Veldkamp; Rita Gerardy-Schahn; Ingrid De Vries; Larry G. Williams; Gary R. Chaffee; Andrew J. Phillips; Friedrich Freiberger; Richard Imre; Deni Taleski; Richard J. Payne; Asolina Braun; Reinhold Förster; Karl Mechtler; Martina Mühlenhoff; Brian F. Volkman; Michael Sixt

doi:10.1126/science.aad0512

Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Eva Kiermaier, Christine Moussion, Christopher T. Veldkamp, Rita Gerardy-Schahn, Ingrid De Vries, Larry G. Williams, Gary R. Chaffee, Andrew J. Phillips, Friedrich Freiberger, Richard Imre, Deni Taleski, Richard J. Payne, Asolina Braun, Reinhold Förster, Karl Mechtler, Martina Mühlenhoff, Brian F. Volkman, Michael Sixt

Research output: Contribution to journal › Article › Research › peer-review

129 Citations (Scopus)

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.

Original language	English
Pages (from-to)	186-190
Number of pages	5
Journal	Science
Volume	351
Issue number	6269
DOIs	https://doi.org/10.1126/science.aad0512
Publication status	Published - 8 Jan 2016
Externally published	Yes

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Kiermaier, E., Moussion, C., Veldkamp, C. T., Gerardy-Schahn, R., De Vries, I., Williams, L. G., Chaffee, G. R., Phillips, A. J., Freiberger, F., Imre, R., Taleski, D., Payne, R. J., Braun, A., Förster, R., Mechtler, K., Mühlenhoff, M., Volkman, B. F., & Sixt, M. (2016). Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science, 351(6269), 186-190. https://doi.org/10.1126/science.aad0512

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title = "Polysialylation controls dendritic cell trafficking by regulating chemokine recognition",

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.",

author = "Eva Kiermaier and Christine Moussion and Veldkamp, {Christopher T.} and Rita Gerardy-Schahn and {De Vries}, Ingrid and Williams, {Larry G.} and Chaffee, {Gary R.} and Phillips, {Andrew J.} and Friedrich Freiberger and Richard Imre and Deni Taleski and Payne, {Richard J.} and Asolina Braun and Reinhold F{\"o}rster and Karl Mechtler and Martina M{\"u}hlenhoff and Volkman, {Brian F.} and Michael Sixt",

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Kiermaier, E, Moussion, C, Veldkamp, CT, Gerardy-Schahn, R, De Vries, I, Williams, LG, Chaffee, GR, Phillips, AJ, Freiberger, F, Imre, R, Taleski, D, Payne, RJ, Braun, A, Förster, R, Mechtler, K, Mühlenhoff, M, Volkman, BF & Sixt, M 2016, 'Polysialylation controls dendritic cell trafficking by regulating chemokine recognition', Science, vol. 351, no. 6269, pp. 186-190. https://doi.org/10.1126/science.aad0512

TY - JOUR

T1 - Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

AU - Kiermaier, Eva

AU - Moussion, Christine

AU - Veldkamp, Christopher T.

AU - Gerardy-Schahn, Rita

AU - De Vries, Ingrid

AU - Williams, Larry G.

AU - Chaffee, Gary R.

AU - Phillips, Andrew J.

AU - Freiberger, Friedrich

AU - Imre, Richard

AU - Taleski, Deni

AU - Payne, Richard J.

AU - Braun, Asolina

AU - Förster, Reinhold

AU - Mechtler, Karl

AU - Mühlenhoff, Martina

AU - Volkman, Brian F.

AU - Sixt, Michael

PY - 2016/1/8

Y1 - 2016/1/8

N2 - 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.

AB - 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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SN - 0036-8075

VL - 351

SP - 186

EP - 190

JO - Science

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ER -

Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Abstract

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