The macromolecular architecture of platelet-derived microparticles

Adi Tamir, Simona Sorrentino, Sarah Motahedeh, Ela Shai, Anna Dubrovsky, Idit Dahan, Matthias Eibauer, Jan Dirk Studt, K. Tanuj Sapra, David Varon, Ohad Medalia

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Platelets are essential for hemostasis and wound healing. They are involved in fundamental processes of vascular biology such as angiogenesis, tissue regeneration, and tumor metastasis. Upon activation, platelets shed small plasma membrane vesicles termed platelet-derived microparticles (PMPs). PMPs include functional cell adhesion machinery that comprises transmembrane receptors (most abundant are the αIIbβ3 integrins), cytoskeletal systems and a large variety of adapter and signaling molecules. Glanzmann thrombasthenia (GT) is a condition characterized by platelets that are deficient of the integrin αIIbβ3 heterodimer. Here, we use cryo-electron tomography (cryo-ET) to study the structural organization of PMPs (in both healthy and GT patients), especially the cytoskeleton organization and receptor architecture. PMPs purified from GT patients show a significantly altered cytoskeletal organization, characterized by a reduced number of filaments present, compared to the healthy control. Furthermore, our results show that incubating healthy PMPs with manganese ions (Mn2+), in the presence of fibrinogen, induces a major conformational change of integrin receptors, whereas thrombin activation yields a moderate response. These results provide the first insights into the native molecular organization of PMPs.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalJournal of Structural Biology
Volume193
Issue number3
DOIs
StatePublished - 1 Mar 2016

Keywords

  • Cryo-electron tomography

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