The macromolecular architecture of platelet-derived microparticles

Journal of Structural Biology
Adi TamirOhad Medalia

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 (Mn(2+)), in the presence of fibrinogen, induces a major conformational change of integrin receptors, whereas thrombin activation yields a moderate response. These res...Continue Reading

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Citations

Apr 23, 2016·Cell Adhesion & Migration·Simona SorrentinoK Tanuj Sapra
Oct 28, 2016·Scientific Reports·Geneviève MarcouxEric Boilard
Sep 7, 2018·Frontiers in Cardiovascular Medicine·Annemiek Dickhout, Rory R Koenen
Nov 20, 2019·Nature Methods·Mauricio Toro-NahuelpanJulia Mahamid
May 26, 2018·Current Opinion in Cell Biology·Meltem Tatli, Ohad Medalia
Sep 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Simona SorrentinoOhad Medalia

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