title: Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins.
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 (alphaLbeta2) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein-fused and yellow fluorescent protein-fused alphaL and beta2 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 alpha and beta cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.
mesh_terms: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D040881:CD11a Antigen / Q000737:chemistry*; D018821:CD18 Antigens / Q000737:chemistry*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry*; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008164:Luminescent Proteins; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019718:Receptors, CXCR4 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015398:Signal Transduction; D016608:Talin / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D040881:CD11a Antigen; D018821:CD18 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D008024:Ligands; D008164:Luminescent Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D016608:Talin; C054562:yellow fluorescent protein, Bacteria; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins