Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity


Cambi, Alessandra and Joosten, Ben and Koopman, Marjolein and Lange, Frank de and Beeren, Inge and Torensma, Ruurd and Fransen, Jack A. and Garcia-Parajo, Maria and Leeuwen, Frank N. van and Figdor, Carl G. (2006) Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity. Molecular biology of the cell, 17 (10). pp. 4270-4281. ISSN 1059-1524

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Abstract:The β2-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
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Copyright:© 2006 by The American Society for Cell Biology
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