Affiliation:
1. CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Abstract
Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 (α
L
β
2
) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein–fused and yellow fluorescent protein–fused α
L
and β
2
cytoplasmic domains. In the resting state these domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the α and β cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
678 articles.
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