Physical proximity and functional interplay of the glycoprotein Ib-IX-V complex and the Fc receptor Fcγ/RIIa on the platelet plasma membrane

Paul M. Sullam, William C. Hyun, Janos Szöllösi, Jing Fei Dong, Wendy M. Foss, José A. López

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Although the glycoprotein (GP) Ib-IX-V complex and FcγRIIA are distinct platelet membrane receptors, previous studies have suggested that these structures may be co-localized. To determine more directly the proximity of GP Ib-IX-V and FcγRIIA, we assessed the effects of anti-GP Ibα monoclonal antibodies on FcγRIIA-mediated platelet aggregation and on the direct binding of polymeric IgG to human platelets. In addition, we directly examined the proximity of FcγRII and GP Ib-IX-V using flow cytometric fluorescence energy transfer and immunoprecipitation studies. Preincubation of platelets with either of two monoclonal antibodies (AN51 or SZ2) directed against GP Ibα completely blocked platelet aggregation by polymeric IgG. Similarly, these antibodies totally inhibited platelet aggregation by two strains of viridans group streptococci known to induce aggregation via FcγRIIA. In addition, AN51 and SZ2 significantly reduced the binding of polymeric IgG to washed fixed platelets. When assessed by flow cytometry, significant levels of bidirectional energy transfer were detected between FcγRIIA and GP Ibα, indicating a physical proximity of less than 10 nm between these receptors. This energy transfer was not due to high receptor density, because no homoassociative energy transfer was seen. Moreover, immunoprecipitation of FcγRIIA from platelet lysates also co-precipitated GP Ibα. These results indicate that GP Ibα and FcγRIIA are co-localized on the platelet membrane and that this association is not random.

Original languageEnglish
Pages (from-to)5331-5336
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
Publication statusPublished - Feb 27 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Physical proximity and functional interplay of the glycoprotein Ib-IX-V complex and the Fc receptor Fcγ/RIIa on the platelet plasma membrane'. Together they form a unique fingerprint.

  • Cite this