Organization of the integrin LFA-1 in nanoclusters regulates its activity

Alessandra Cambi, Ben Joosten, Marjolein Koopman, Frank de Lange, Inge Beeren, Ruurd Torensma, Jack A Fransen, Maria Garcia-Parajó, Frank N van Leeuwen, Carl G Figdor

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

Abstract

The beta2-integrin LFA-1 facilitates extravasation of monocytes (MOs) into the underlying tissues, where MOs can differentiate into dendritic cells (DCs). Although DCs express LFA-1, unlike MOs, they cannot bind to ICAM-1. We hypothesized that an altered integrin organization on the DC plasma membrane might cause this effect and investigated the relationship between membrane organization and function of LFA-1 on MOs and DCs. High-resolution mapping of LFA-1 surface distribution revealed that on MOs LFA-1 function is associated with a distribution in well-defined nanoclusters (100-150-nm diameter). Interestingly, a fraction of these nanoclusters contains primed LFA-1 molecules expressing the specific activation-dependent L16-epitope. Live imaging of MO-T-cell conjugates showed that only these primed nanoclusters are dynamically recruited to the cellular interface forming micrometer-sized assemblies engaged in ligand binding and linked to talin. We conclude that besides affinity regulation, LFA-1 function is controlled by at least three different avidity patterns: random distributed inactive molecules, well-defined ligand-independent proactive nanoclusters, and ligand-triggered micrometer-sized macroclusters.

Original languageEnglish
Pages (from-to)4270-81
Number of pages12
JournalMolecular biology of the cell
Volume17
Issue number10
DOIs
Publication statusPublished - Oct 2006
Externally publishedYes

Keywords

  • Cell Adhesion
  • Cell Aggregation
  • Cell Membrane/metabolism
  • Dendritic Cells/physiology
  • Humans
  • Intercellular Adhesion Molecule-1/metabolism
  • Lymphocyte Function-Associated Antigen-1/metabolism
  • Membrane Microdomains/physiology
  • Models, Biological
  • Monocytes/physiology
  • T-Lymphocytes/physiology

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