Structural analysis of receptors and actin polarity in platelet protrusions
During activation the platelet cytoskeleton is reorganized, inducing adhesion to the extracellular matrix and cell spreading. These processes are critical for wound healing and clot formation. Initially, this task relies on the formation of strong cellular–extracellular matrix interactions, exposed...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2021-09, Vol.118 (37), p.1-8 |
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| creator | Sorrentino, Simona Conesa, Jose Javier Cuervo, Ana Melero, Roberto Martins, Bruno Fernandez-Gimenez, Estrella P. de Isidro-Gomez, Federico de la Morena, Jimenez Studt, Jan-Dirk Sorzano, Carlos Oscar S. Eibauer, Matthias Carazo, Jose Maria Medalia, Ohad |
| description | During activation the platelet cytoskeleton is reorganized, inducing adhesion to the extracellular matrix and cell spreading. These processes are critical for wound healing and clot formation. Initially, this task relies on the formation of strong cellular–extracellular matrix interactions, exposed in subendothelial lesions. Despite the medical relevance of these processes, there is a lack of high-resolution structural information on the platelet cytoskeleton controlling cell spreading and adhesion. Here, we present in situ structural analysis of membrane receptors and the underlying cytoskeleton in platelet protrusions by applying cryoelectron tomography to intact platelets. We utilized three-dimensional averaging procedures to study receptors at the plasma membrane. Analysis of substrate interaction-free receptors yielded one main structural class resolved to 26 Å, resembling the αIIbβ₃ integrin folded conformation. Furthermore, structural analysis of the actin network in pseudopodia indicates a nonuniform polarity of filaments. This organization would allow generation of the contractile forces required for integrin-mediated cell adhesion. |
| doi_str_mv | 10.1073/pnas.2105004118 |
| format | Article |
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These processes are critical for wound healing and clot formation. Initially, this task relies on the formation of strong cellular–extracellular matrix interactions, exposed in subendothelial lesions. Despite the medical relevance of these processes, there is a lack of high-resolution structural information on the platelet cytoskeleton controlling cell spreading and adhesion. Here, we present in situ structural analysis of membrane receptors and the underlying cytoskeleton in platelet protrusions by applying cryoelectron tomography to intact platelets. We utilized three-dimensional averaging procedures to study receptors at the plasma membrane. Analysis of substrate interaction-free receptors yielded one main structural class resolved to 26 Å, resembling the αIIbβ₃ integrin folded conformation. Furthermore, structural analysis of the actin network in pseudopodia indicates a nonuniform polarity of filaments. This organization would allow generation of the contractile forces required for integrin-mediated cell adhesion.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2105004118</identifier><identifier>PMID: 34504018</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Actin ; Actin Cytoskeleton ; Actins - chemistry ; Actins - metabolism ; Adhesion ; Biological Sciences ; Blood Platelets - physiology ; Cell Adhesion ; Cell Membrane - metabolism ; Cell spreading ; Cell Surface Extensions - physiology ; Conformation ; Contractility ; Cytoskeleton ; Extracellular matrix ; Filaments ; Humans ; Membranes ; Platelet Activation ; Platelet Glycoprotein GPIIb-IIIa Complex - chemistry ; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism ; Platelets ; Polarity ; Pseudopodia ; Receptors ; Structural analysis ; Substrates ; Wound healing</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-09, Vol.118 (37), p.1-8</ispartof><rights>Copyright © 2021 the Author(s). Published by PNAS.</rights><rights>Copyright National Academy of Sciences Sep 14, 2021</rights><rights>Copyright © 2021 the Author(s). 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| subjects | Actin Actin Cytoskeleton Actins - chemistry Actins - metabolism Adhesion Biological Sciences Blood Platelets - physiology Cell Adhesion Cell Membrane - metabolism Cell spreading Cell Surface Extensions - physiology Conformation Contractility Cytoskeleton Extracellular matrix Filaments Humans Membranes Platelet Activation Platelet Glycoprotein GPIIb-IIIa Complex - chemistry Platelet Glycoprotein GPIIb-IIIa Complex - metabolism Platelets Polarity Pseudopodia Receptors Structural analysis Substrates Wound healing |
| title | Structural analysis of receptors and actin polarity in platelet protrusions |
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