Organization of the integrin LFA-1 in nanoclusters regulates its activity.
SourceMolecular Biology of the Cell, 17, 10, (2006), pp. 4270-4281
Article / Letter to editor
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Cell Biology (UMC)
Molecular Biology of the Cell
SubjectIGMD 8: Mitochondrial medicine; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; NCMLS 3: Tissue engineering and pathology; NCMLS 5: Membrane transport and intracellular motility; ONCOL 2: Age-related aspects of cancer; ONCOL 3: Translational research; UMCN 4.1: Microbial pathogenesis and host defense; UMCN 5.3: Cellular energy metabolism
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.
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