Extracellular matrix-specific platelet activation leads to a differential translational response and protein de novo synthesis in human platelets

  • Platelets are exposed to extracellular matrix (ECM) proteins like collagen and laminin and to fibrinogen during acute vascular events. However, beyond hemostasis, platelets have the important capacity to migrate on ECM surfaces, but the translational response of platelets to different extracellular matrix stimuli is still not fully characterized. Using 2D-gel electrophoresis, confocal microscopy, polysome analysis and protein sequencing by mass spectrometry, we demonstrate that platelets show a differential expression profile of newly synthesized proteins on laminin, collagen or fibrinogen. In this context, we observed a characteristic, ECM-dependent translocation phenotype of translation initiation factor eIF4E to the ribosomal site. eIF4E accumulated in polysomes with increased binding of mRNA and co-localization with vinculin, leading to de novo synthesis of important cytoskeletal regulator proteins. As the first study, we included a proteome analysis of laminin-adherent plateletsPlatelets are exposed to extracellular matrix (ECM) proteins like collagen and laminin and to fibrinogen during acute vascular events. However, beyond hemostasis, platelets have the important capacity to migrate on ECM surfaces, but the translational response of platelets to different extracellular matrix stimuli is still not fully characterized. Using 2D-gel electrophoresis, confocal microscopy, polysome analysis and protein sequencing by mass spectrometry, we demonstrate that platelets show a differential expression profile of newly synthesized proteins on laminin, collagen or fibrinogen. In this context, we observed a characteristic, ECM-dependent translocation phenotype of translation initiation factor eIF4E to the ribosomal site. eIF4E accumulated in polysomes with increased binding of mRNA and co-localization with vinculin, leading to de novo synthesis of important cytoskeletal regulator proteins. As the first study, we included a proteome analysis of laminin-adherent platelets and interestingly identified upregulation of essentially important proteins that mediate cytoskeletal regulation and mobility in platelets, such as filamin A, talin, vinculin, gelsolin, coronin or kindlin-3. In summary, we demonstrate that platelet activation with extracellular matrix proteins results in a distinct stimulus-specific translational response of platelets that will help to improve our understanding of the regulation of platelet mobility and migration.show moreshow less

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Metadaten
Author:Bjoern F. Kraemer, Marc Geimer, Mirita Franz-Wachtel, Tobias Lamkemeyer, Hanna MannellGND, Stephan Lindemann
URN:urn:nbn:de:bvb:384-opus4-1080174
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/108017
ISSN:1422-0067OPAC
Parent Title (English):International Journal of Molecular Sciences
Publisher:MDPI
Place of publication:Basel
Type:Article
Language:English
Year of first Publication:2020
Publishing Institution:Universität Augsburg
Release Date:2023/09/25
Tag:Inorganic Chemistry; Organic Chemistry; Physical and Theoretical Chemistry; Computer Science Applications; Spectroscopy; Molecular Biology; General Medicine; Catalysis
Volume:21
Issue:21
First Page:8155
DOI:https://doi.org/10.3390/ijms21218155
Institutes:Medizinische Fakultät
Medizinische Fakultät / Lehrstuhl für Physiologie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)