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J Cell Sci. 2018 Oct 2;131(19). pii: jcs214551. doi: 10.1242/jcs.214551.

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

Author information

1
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, 6525 GA Nijmegen, The Netherlands.
2
MRC Laboratory of Molecular Cell Biology, University College London, London WC1E 6BT, UK.
3
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
4
Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
5
Institute for Physiological Chemistry and Pathobiochemistry, D-48149 Münster, Germany.
6
University Clinic of Würzburg and Rudolf Virchow Center for Experimental Biomedicine, 97070 Würzburg, Germany.
7
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
8
Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands, UK.
9
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Tumor Immunology, 6525 GA Nijmegen, The Netherlands annemiek.vanspriel@radboudumc.nl.

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.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

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

PMID:
30185523
DOI:
10.1242/jcs.214551
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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