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

Acton, SE; De Winde, C; (2018) C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37. Journal of Cell Science , 131 , Article jcs214551. 10.1242/jcs.214551. Green open access

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Abstract

Cell migration is central to 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 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 into the mechanisms underlying CLEC-2-dependent DC migration.

Type: Article
Title: C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.214551
Publisher version: https://doi.org/10.1242/jcs.214551
Language: English
Additional information: This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CLEC-2, Dendritic cell, Migration, Membrane organization, Tetraspanin
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10054920
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