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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / metabolism*
  • Cell Adhesion
  • Cell Movement*
  • Cell Surface Extensions / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism*
  • Endothelial Cells / metabolism
  • HEK293 Cells
  • Humans
  • Interleukin-6 / biosynthesis
  • Lectins, C-Type / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / metabolism
  • Protein Binding
  • RAW 264.7 Cells
  • Tetraspanins / deficiency
  • Tetraspanins / metabolism*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • CD37 protein, human
  • CLEC-2 protein, mouse
  • CLEC2B protein, human
  • Cd37 protein, mouse
  • Interleukin-6
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Tetraspanins
  • Actomyosin