Intermolecular transmembrane domain interactions activate integrin αIIbβ3.
Integrins are the major cell adhesion molecules responsible for cell attachment to the extracellular matrix. The strength of integrin-mediated adhesion is controlled by the affinity of individual integrins (integrin activation) as well as by the number of integrins involved in such adhesion. The positive correlation between integrin activation and integrin clustering had been suggested previously, but several trials to induce integrin clustering by dimerization of the transmembrane domain or tail region of integrin α subunits failed to demonstrate any change in integrin activation. Here, using platelet integrin αIIbβ3 as a model system, we showed that there is intermolecular lateral interaction between integrins through the transmembrane domains, and this interaction can enhance the affinity state of integrins. In addition, when integrin clustering was induced through heteromeric lateral interactions using bimolecular fluorescence complementation, we could observe a significant increase in the number of active integrin molecules. Because the possibility of intermolecular interaction would be increased by a higher local concentration of integrins, we propose that integrin clustering can shift the equilibrium in favor of integrin activation.
From the Department of Medicine, University of California San Diego, La Jolla, California 92093 and.
Feng
F
Ye
the School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Se-Jong
SJ
Kim
the School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea chungho@korea.ac.kr.
Chungho
C
Kim
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D019039:Platelet Glycoprotein GPIIb-IIIa Complex
Bimolecular Fluorescence Complementation; Fluorescence; Integrin; Integrin Activation; Integrin Clustering; Platelet; Protein-Protein interaction; Thrombosis; Transmembrane Domain