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

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Cell migration is centralto evoking 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; encoded by the gene Clec1b), expressed by DCs, with podoplanin, expressed by lymph node stromal cells, although the underlying 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 displacementonlymph nodestromal cells. Moreover, Cd37-/- DCs failedto form actin protrusions in a 3Dcollagen 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 into the mechanisms underlying CLEC-2-dependent DC migration. This article has an associated First Person interview with the first author of the paper.

Original languageEnglish
Article numberjcs.214551
JournalJournal of Cell Science
Issue number19
Publication statusPublished - 1 Oct 2018
Externally publishedYes


  • CLEC-2
  • Dendritic cell
  • Membrane organization
  • Migration
  • Tetraspanin

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