Abstract
Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/ or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside–out signaling mechanisms for β1 integrins.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:49 p.m.) |
Deposited | 2 years, 1 month ago (July 25, 2023, 4:35 a.m.) |
Indexed | 1 month, 4 weeks ago (July 2, 2025, 2:45 p.m.) |
Issued | 27 years, 10 months ago (Oct. 20, 1997) |
Published | 27 years, 10 months ago (Oct. 20, 1997) |
Published Online | 27 years, 10 months ago (Oct. 20, 1997) |
Published Print | 27 years, 10 months ago (Oct. 20, 1997) |
@article{Yauch_1997, title={Mutational Evidence for Control of Cell Adhesion Through Integrin Diffusion/Clustering, Independent of Ligand Binding}, volume={186}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.186.8.1347}, DOI={10.1084/jem.186.8.1347}, number={8}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Yauch, Robert L. and Felsenfeld, Dan P. and Kraeft, Stine-Kathrein and Chen, Lan Bo and Sheetz, Michael P. and Hemler, Martin E.}, year={1997}, month=oct, pages={1347–1355} }