The involvement of lipid rafts in the regulation of integrin function

B Leitinger, N Hogg - Journal of cell science, 2002 - journals.biologists.com
B Leitinger, N Hogg
Journal of cell science, 2002journals.biologists.com
Integrin activity on cells such as T lymphocytes is tightly controlled. Here we demonstrate a
key role for lipid rafts in regulating integrin function. Without stimulation integrin LFA-1 is
excluded from lipid rafts, but following activation LFA-1 is mobilised to the lipid raft
compartment. An LFA-1 construct from which the I domain has been deleted mimics
activated integrin and is constitutively found in lipid rafts. This correlation between integrin
activation and raft localisation extends to a second integrin, α4β1, and the clustering of α4β1 …
Integrin activity on cells such as T lymphocytes is tightly controlled. Here we demonstrate a key role for lipid rafts in regulating integrin function. Without stimulation integrin LFA-1 is excluded from lipid rafts, but following activation LFA-1 is mobilised to the lipid raft compartment. An LFA-1 construct from which the I domain has been deleted mimics activated integrin and is constitutively found in lipid rafts. This correlation between integrin activation and raft localisation extends to a second integrin,α4β1, and the clustering of α4β1 is also raft dependent. Both LFA-1 and α4β1-mediated adhesion is dependent upon intact lipid rafts providing proof of the functional relevance of the lipid raft localisation. Finally we find that non-raft integrins are excluded from the rafts by cytoskeletal constraints. The presence of integrin in lipid rafts under stimulating conditions that activate these receptors strongly indicates that the rafts have a key role in positively regulating integrin activity.
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