C-type lectin-like receptor 2 (CLEC-2)-dependent dendritic cell 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, Michael G. Tomlinson, Sophie E. Acton, Annemiek B. Van Spriel

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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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, although the molecular mechanisms remain elusive. Here, we show that CLEC-2-dependent DC migration is controlled by tetraspanin CD37, a membrane-organizing protein. We identified a specific interaction between CLEC-2 and CD37, and myeloid cells lacking CD37 (Cd37-/-) expressed reduced surface CLEC-2. CLEC-2-expressing Cd37-/- DCs showed impaired adhesion, migration velocity and displacement on lymph node stromal cells. Moreover, Cd37-/- DCs failed to form actin protrusions in a 3D collagen matrix upon podoplanin-induced CLEC-2 stimulation, phenocopying CLEC-2-deficient DCs. Microcontact printing experiments revealed that CD37 is required for CLEC-2 recruitment in the membrane to its ligand podoplanin. Finally, Cd37-/- DCs failed to inhibit actomyosin contractility in lymph node stromal cells, thus phenocopying CLEC-2-deficient DCs. This study demonstrates that tetraspanin CD37 controls CLEC-2 membrane organization and provides new molecular insights underlying CLEC-2-dependent DC migration.
Original languageEnglish
Article numberjcs214551
Number of pages15
JournalJournal of Cell Science
Volume131
Issue number19
Early online date5 Sep 2018
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • CLEC-2
  • dendritic cell
  • migration
  • membrane organization
  • tetraspanin

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