PMID:9190212

Citation	Lub, M, van Kooyk, Y, van Vliet, SJ and Figdor, CG (1997) Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1. Mol. Biol. Cell 8:341-51
Abstract	Intracellular signals are required to activate the leukocyte-specific adhesion receptor lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) to bind its ligand, intracellular adhesion molecule-1 (ICAM-1). In this study, we investigated the role of the cytoskeleton in LFA-1 activation and demonstrate that filamentous actin (F-actin) can both enhance and inhibit LFA-1-mediated adhesion, depending on the distribution of LFA-1 on the cell surface. We observed that LFA-1 is already clustered on the cell surface of interleukin-2/phytohemagglutinin-activated lymphocytes. These cells bind strongly ICAM-1 and disruption of the actin cytoskeleton inhibits adhesion. In contrast to interleukin-2/phytohemagglutinin-activated peripheral blood lymphocytes, resting lymphocytes, which display a homogenous cell surface distribution of LFA-1, respond poorly to intracellular signals to bind ICAM-1, unless the actin cytoskeleton is disrupted. On resting peripheral blood lymphocytes, uncoupling of LFA-1 from the actin cytoskeleton induces clustering of LFA-1 and this, along with induction of a high-affinity form of LFA-1, via "inside-out" signaling, results in enhanced binding to ICAM-1, which is dependent on intact intermediate filaments, microtubules, and metabolic energy. We hypothesize that linkage of LFA-1 to cytoskeletal elements prevents movement of LFA-1 over the cell surface, thus inhibiting clustering and strong ligand binding. Release from these cytoskeletal elements allows lateral movement and activation of LFA-1, resulting in ligand binding and "outside-in" signaling, that subsequently stimulates actin polymerization and stabilizes cell adhesion.
Links	PubMed PMC276084
Keywords	Actin Cytoskeleton/metabolism; Actins/physiology; Animals; Cell Adhesion/physiology; Cytochalasin D/pharmacology; Cytoskeleton/physiology; Fibroblasts; Humans; Intercellular Adhesion Molecule-1/metabolism; Intermediate Filaments/metabolism; L Cells (Cell Line); Leukocytes/metabolism; Lymphocyte Function-Associated Antigen-1/physiology; Melanoma; Mice; Microtubules/metabolism; Protein Binding; Tumor Cells, Cultured
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TARA		GO:0015629: actin cytoskeleton	ECO:0000314:		C		In this study, the role of the cytoskeleton in LFA-1 activation and demonstrate that filamentous actin (F-actin) was shown to both enhance and inhibit LFA-1-mediated adhesion, depending on the distribution of LFA-1 on the cell surface.	complete CACAO 9456

References

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