The macromolecular architecture of platelet-derived microparticles.

作者: Adi Tamir , Simona Sorrentino , Sarah Motahedeh , Ela Shai , Anna Dubrovsky

DOI: 10.1016/J.JSB.2015.12.013

关键词:

摘要: Platelets are essential for hemostasis and wound healing. They involved in fundamental processes of vascular biology such as angiogenesis, tissue regeneration, 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 the αIIbβ3 integrins), cytoskeletal systems a large variety adapter signaling molecules. Glanzmann thrombasthenia (GT) is condition characterized by deficient integrin heterodimer. Here, we use cryo-electron tomography (cryo-ET) to study structural organization (in both healthy GT patients), especially cytoskeleton receptor architecture. purified from patients show significantly altered organization, reduced number filaments present, compared control. Furthermore, our results incubating with manganese ions (Mn(2+)), presence fibrinogen, induces major conformational change receptors, whereas thrombin activation yields moderate response. These provide first insights into native molecular PMPs.

参考文章(54)
J H McAnulty, S H Goodnight, L M Taylor, B M Coull, Antiplatelet therapy--Part II. Western Journal of Medicine. ,vol. 158, pp. 506- 514 ,(1993)
CL Wagner, MA Mascelli, DS Neblock, HF Weisman, BS Coller, RE Jordan, Analysis of GPIIb/IIIa Receptor Number by Quantification of 7E3 Binding to Human Platelets Blood. ,vol. 88, pp. 907- 914 ,(1996) , 10.1182/BLOOD.V88.3.907.907
J Gailit, E Ruoslahti, Regulation of the fibronectin receptor affinity by divalent cations. Journal of Biological Chemistry. ,vol. 263, pp. 12927- 12932 ,(1988) , 10.1016/S0021-9258(18)37650-6
Mark L. Kahn, Yao-Wu Zheng, Wei Huang, Violeta Bigornia, Dewan Zeng, Stephen Moff, Robert V. Farese, Carmen Tam, Shaun R. Coughlin, A dual thrombin receptor system for platelet activation Nature. ,vol. 394, pp. 690- 694 ,(1998) , 10.1038/29325
JN George, JP Caen, AT Nurden, Glanzmann's thrombasthenia: the spectrum of clinical disease Blood. ,vol. 75, pp. 1383- 1395 ,(1990) , 10.1182/BLOOD.V75.7.1383.BLOODJOURNAL7571383
Benjamin A. Garcia, David M. Smalley, Cho, Jeffrey Shabanowitz, Klaus Ley, Donald F. Hunt, The platelet microparticle proteome. Journal of Proteome Research. ,vol. 4, pp. 1516- 1521 ,(2005) , 10.1021/PR0500760
Feng Ye, Jun Liu, Hanspeter Winkler, Kenneth A. Taylor, Integrin αIIbβ3 in a Membrane Environment Remains the Same Height after Mn2+ Activation when Observed by Cryoelectron Tomography Journal of Molecular Biology. ,vol. 378, pp. 976- 986 ,(2008) , 10.1016/J.JMB.2008.03.014
J H Hartwig, Mechanisms of actin rearrangements mediating platelet activation. Journal of Cell Biology. ,vol. 118, pp. 1421- 1442 ,(1992) , 10.1083/JCB.118.6.1421
Israel Patla, Tova Volberg, Nadav Elad, Vera Hirschfeld-Warneken, Carsten Grashoff, Reinhard Fässler, Joachim P. Spatz, Benjamin Geiger, Ohad Medalia, Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography Nature Cell Biology. ,vol. 12, pp. 909- 915 ,(2010) , 10.1038/NCB2095
Simona Sorrentino, Jan-Dirk Studt, Ohad Medalia, K. Tanuj Sapra, Roll, adhere, spread and contract: structural mechanics of platelet function. European Journal of Cell Biology. ,vol. 94, pp. 129- 138 ,(2015) , 10.1016/J.EJCB.2015.01.001