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

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 mecha...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors De Winde, Charlotte M, Matthews, Alexandra L, Sjoerd Van Deventer, Alie Van Der Schaaf, Tomlinson, Neil D, Jansen, Erik, Eble, Johannes A, Nieswandt, Bernhard, Mcgettrick, Helen M, Figdor, Carl G, Acton, Sophie E, Tomlinson, Michael G, Van Spriel, Annemiek B
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 22.12.2017
Subjects
Actin
CD11c antigen
Cell adhesion & migration
Cell migration
Cell surface
Collagen
Dendritic cells
Lymph nodes
Membrane proteins
Molecular modelling
Myeloid cells
Stromal cells
Online AccessGet full text

Cover

More Information
Summary: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 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.
DOI:10.1101/227918