title: The macromolecular architecture of platelet-derived microparticles.
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 results provide the first insights into the native molecular organization of PMPs.
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva 84105, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Tamir
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Simona
authors.initials: S
authors.lastname: Sorrentino
authors.affiliation: Coagulation Unit, Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Motahedeh
authors.affiliation: Coagulation Unit, Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Ela
authors.initials: E
authors.lastname: Shai
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubrovsky
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva 84105, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Dahan
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eibauer
authors.affiliation: Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Jan-Dirk
authors.initials: JD
authors.lastname: Studt
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: K Tanuj
authors.initials: KT
authors.lastname: Sapra
authors.affiliation: Coagulation Unit, Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Varon
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva 84105, Israel; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: omedalia@bioc.uzh.ch.
authors.forename: Ohad
authors.initials: O
authors.lastname: Medalia
mesh_terms: D001792:Blood Platelets / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion / Q000235:genetics; D055252:Cell-Derived Microparticles / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008345:Manganese / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D013915:Thrombasthenia / Q000097:blood* / Q000473:pathology; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D008345:Manganese; D005340:Fibrinogen; D013917:Thrombin
keywords: Cryo-electron tomography