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

Cambi A, Joosten B, Koopman M, de Lange F, Beeren I, Torensma R, Fransen JA, Garcia-Parajó M, van Leeuwen FN, Figdor CG.
Mol Biol Cell. 2006 Oct;17(10):4270-81. Epub 2006 Jul 19.

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.

URL: http://www.molbiolcell.org/cgi/content/full/17/10/4270

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/16855029

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