Published 20 December 2004. doi:10.1083/jcb1676iti3
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 6, 992-993
Clustering in integrin binding
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Integrin clustering helps strengthen existing adhesions.
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The adhesiveness of integrin binding is determined by both the affinity of individual heterodimers for their ligand and the clustering of multiple heterodimers. Kim et al. show, on page 1241, that clustering does not precede binding but rather functions in adhesion strengthening following binding to multivalent ligands.To probe the question of whether clustering or affinity are primary factors in leukocyte integrin binding, Kim et al. devised a FRET system in which either the 
or ß subunits of the integrin LFA-1 (Lß2) were labeled with nondimerizing forms of YFP and CFP. Under basal conditions, no micro-clustering was evident, as cells expressing L-mCFP, L-mYFP, and wild-type ß2 showed little FRET. Nor did the researchers observe FRET when cells were stimulated to activate LFA-1 adhesiveness. Furthermore, activation of LFA-1 with cytoskeletal-disrupting agents did not induce microclusters or macroclusters, visible by confocal microscopy, in the absence of multivalent ligands.
However, addition of multivalent (but not monovalent) ICAM-1 ligand to stimulated cells induced FRET. Macro- and microclusters did form when cells expressing both the ligand and the integrin heterodimer were cultured together in a manner that stimulated aggregation.
Kim et al. conclude that clustering is involved in strengthening the adhesion force, after initial binding of a multivalent ligand. They hypothesize that conformational changes within the integrin heterodimer—which they were able to confirm with intramolecular FRET—is the key factor in activating integrin adhesiveness. 
Rabiya Tuma
rabiya{at}nasw.org
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