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C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37

Charlotte M de Winde, Alexandra L Matthews, Sjoerd van Deventer, Alie van der Schaaf, Neil D Tomlinson, Erik Jansen, Johannes A Eble, Bernhard Nieswandt, Helen M McGettrick, Carl G Figdor, Sophie E Acton, Michael G Tomlinson, Annemiek B van Spriel
doi: https://doi.org/10.1101/227918
Charlotte M de Winde
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.MRC Laboratory of Molecular Cell Biology, University College London, London, United Kingdom.
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Alexandra L Matthews
School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
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Sjoerd van Deventer
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
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Alie van der Schaaf
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
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Neil D Tomlinson
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom.
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Erik Jansen
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
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Johannes A Eble
Institute for Physiological Chemistry and Pathobiochemistry, Münster, Germany.
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Bernhard Nieswandt
University Clinic of Würzburg & Rudolf Virchow Center, Würzburg, Germany.
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Helen M McGettrick
Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
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Carl G Figdor
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
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Sophie E Acton
MRC Laboratory of Molecular Cell Biology, University College London, London, United Kingdom.
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Michael G Tomlinson
School of Biosciences, University of Birmingham, Birmingham, United Kingdom.Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands, United Kingdom.
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Annemiek B van Spriel
Radboud university medical center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
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  • For correspondence: annemiek.vanspriel@radboudumc.nl
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Abstract

Cell migration is central to evoke a potent immune response. Dendritic cell (DC) migration to lymph nodes is dependent on the interaction of C-type lectin-like receptor 2 (CLEC-2) expressed by DCs, with podoplanin expressed by lymph node stromal cells (LNSCs). However, the underlying molecular mechanisms by which CLEC-2 influences DC migration remain elusive. Here, we show that CLEC-2-dependent DC migration is tightly controlled by tetraspanin CD37, a membrane-organizing protein. Our findings demonstrate a specific molecular interaction between CLEC-2 and CD37. Myeloid cells lacking CD37 (Cd37-/-) expressed less CLEC-2 on their surface compared to wild-type cells, indicating that CD37 is required to stabilize membrane expression of CLEC-2. In addition, CLEC-2-expressing DCs lacking CD37 showed impaired adhesion, migration velocity and displacement on LNSCs. Moreover, Cd37-/- DCs failed to form actin protrusions in a 3D collagen matrix upon podoplanin-induced CLEC-2 stimulation, phenocopying CLEC-2-deficient DCs (CD11cΔCLEC-2). Microcontact printing experiments revealed that CD37 is required for CLEC-2 recruitment in the membrane to its ligand podoplanin. This study demonstrates that tetraspanin CD37 controls CLEC-2 membrane organization and provides new molecular insights underlying CLEC-2-dependent DC migration.

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Posted December 22, 2017.
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C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37
Charlotte M de Winde, Alexandra L Matthews, Sjoerd van Deventer, Alie van der Schaaf, Neil D Tomlinson, Erik Jansen, Johannes A Eble, Bernhard Nieswandt, Helen M McGettrick, Carl G Figdor, Sophie E Acton, Michael G Tomlinson, Annemiek B van Spriel
bioRxiv 227918; doi: https://doi.org/10.1101/227918
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C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37
Charlotte M de Winde, Alexandra L Matthews, Sjoerd van Deventer, Alie van der Schaaf, Neil D Tomlinson, Erik Jansen, Johannes A Eble, Bernhard Nieswandt, Helen M McGettrick, Carl G Figdor, Sophie E Acton, Michael G Tomlinson, Annemiek B van Spriel
bioRxiv 227918; doi: https://doi.org/10.1101/227918

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