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

Research output: Contribution to journalArticle

Authors

  • Charlotte M. De Winde
  • Alexandra L. Matthews
  • Sjoerd Van Deventer
  • Alie Van Der Schaaf
  • Neil D. Tomlinson
  • Erik Jansen
  • Johannes A. Eble
  • Bernhard Nieswandt
  • Carl G. Figdor
  • Sophie E. Acton
  • Annemiek B. Van Spriel

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.

Details

Original languageEnglish
Article numberjcs.214551
JournalJournal of Cell Science
Early online date5 Sep 2018
Publication statusE-pub ahead of print - 5 Sep 2018

Keywords

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