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

de Winde, C. M.; Matthews, A. L.; van Deventer, S.; van der Schaaf, A.; Tomlinson, N. D.; Yang, J.; Jansen, E.; Eble, J. A.; Nieswandt, B.; McGettrick, H. M.; Figdor, C. G.; Acton, S. E.; Tomlinson, M. G.; van Spriel, A. B.

doi:10.1101/227918

bioRxiv · 10.1101/227918

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

de Winde, C. M.·Matthews, A. L.·van Deventer, S.·van der Schaaf, A.·Tomlinson, N. D.·Yang, J.·Jansen, E.·Eble, J. A.·Nieswandt, B.·McGettrick, H. M.·Figdor, C. G.·Acton, S. E.·Tomlinson, M. G.·van Spriel, A. B.

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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 (CD11c{Delta}CLEC-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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de Winde, C. M., Matthews, A. L., van Deventer, S., van der Schaaf, A., Tomlinson, N. D., Yang, J., Jansen, E., Eble, J. A., Nieswandt, B., McGettrick, H. M., Figdor, C. G., Acton, S. E., Tomlinson, M. G., van Spriel, A. B.. 2017-12-02. C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37. https://doi.org/10.1101/227918

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