Interactions of platelet integrin αIIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation

Chungho Kim, Tong Lay Lau, Tobias S. Ulmer, Mark H. Ginsberg

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4747-4753
Number of pages7
JournalBlood
Volume113
Issue number19
DOIs
Publication statusPublished - 2009 Nov 17
Externally publishedYes

Fingerprint

Cell membranes
Platelets
Integrins
Blood Platelets
Chemical activation
Cell Membrane
Association reactions
Talin
Membrane Lipids
Hemostasis
Nuclear magnetic resonance spectroscopy
Cluster Analysis
Thrombosis
Magnetic Resonance Spectroscopy
Salts
Lipids
Mutation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Interactions of platelet integrin αIIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation. / Kim, Chungho; Lau, Tong Lay; Ulmer, Tobias S.; Ginsberg, Mark H.

In: Blood, Vol. 113, No. 19, 17.11.2009, p. 4747-4753.

Research output: Contribution to journalArticle

Kim, Chungho ; Lau, Tong Lay ; Ulmer, Tobias S. ; Ginsberg, Mark H. / Interactions of platelet integrin αIIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation. In: Blood. 2009 ; Vol. 113, No. 19. pp. 4747-4753.
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