Clustering and occupancy of platelet integrin αIIbβ 3 (GPIIb-IIIa) generate biologically important signals: conversely, intracellular signals increase the integrins' affinity, leading to integrin activation; both forms of integrin signaling play important roles in hemostasis and thrombosis. Indirect evidence implicates interactions between integrin α and β transmembrane domains (TMDs) and cytoplasmic domains in integrin signaling; however, efforts to directly identify these associations have met with varying and controversial results. In this study, wedevelop mini-integrin affinity capture and use it in combination with nuclear magnetic resonance spectroscopy to show preferential heterodimeric association of integrin αIIbβ3 TMD-tails via specific TMD interactions in mammalian cell membranes and in lipid bicelles. Furthermore, charge reversal mutations at αIIb(R995)β3(D723) confirm a proposed salt bridge and show that it stabilizes the TMD-tail association; talin binding to the β3 tail, which activates the integrin, disrupts this association. These studies establish the preferential heterodimeric interactions of integrin αIIbβ3 TMD-tails in mammalian cell membranes and document their role in integrin signaling.
|Number of pages||7|
|Publication status||Published - 2009|
ASJC Scopus subject areas
- Cell Biology