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Platelet Integrin αIIbβ3: Mechanisms of Activation and Clustering; Involvement into the Formation of the Thrombus Heterogeneous Structure

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

Glycoproteins IIb-IIIa (GPIIb-IIIa), also known as αIIbβ3 integrins, are key platelet adhesion receptors. These molecules are the most abundant (over 10 000 copies per cell) transmembrane receptors playing a crucial role in thrombus formation by promoting platelet aggregation. Integrins need to undergo activation and transit to high-affinity state for their ligands – fibrinogen, fibrin, and von Willebrand factor (VWF) – in order to form bonds between platelets. Activation of integrins is mediated by a set of various messengers through intracellular signalization. Integrins αIIbβ3, like other integrins, are capable of reverse signal transmission inside the cell, called “outside-in” signaling. Recent studies have shown heterogeneity of the thrombus structure and the existence of a stable and dense inner core and a fluid-like loose shell. Since platelet aggregation is provided by integrin-mediated interactions, one can suggest that it is the features of integrin activation and clustering that strongly influence the formation of thrombus architecture. This work is intent on systematizing recent data concerning activation and functioning of platelet integrins αIIbβ3 and searching for correlations between thrombus heterogeneity and the state of integrins on the platelets surface.

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Authors and Affiliations

  1. Faculty of Physics, Moscow Lomonosov State University, 119991, Moscow, Russia

    V. N. Kaneva, A. A. Martyanov, M. A. Panteleev & A. N. Sveshnikova

  2. National Medical Research Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, 117198, Moscow, Russia

    V. N. Kaneva, A. A. Martyanov, M. A. Panteleev & A. N. Sveshnikova

  3. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991, Moscow, Russia

    V. N. Kaneva, A. A. Martyanov, M. A. Panteleev & A. N. Sveshnikova

  4. Faculty of Medicine, Moscow Lomonosov State University, 119991, Moscow, Russia

    D. S. Morozova

  5. Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700, Dolgoprudnyi, Moscow oblast, Russia

    M. A. Panteleev

  6. Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991, Moscow, Russia

    A. N. Sveshnikova

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  1. V. N. Kaneva
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Correspondence to M. A. Panteleev.

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Translated by V. Kaneva

Abbreviations: ADMIDAS, domain adjacent to MIDAS; Btk, Bruton tyrosine kinase; CalDAG-GEFI, Ca2+ and diacylglycerol regulated guanine nucleotide exchange factor I; CHO, Chinese hamster ovary cells; CLEC-2, C-type lectin-like receptor 2; DAG, diacylglycerol; DTS, dense tubular system; EGF, Epidermal Growth Factor; FERM, 4.1 protein, ezrin, radixin, moesin; GPCR, G-protein-coupled receptor; GPIb, glycoprotein Ib; GPVI, glycoprotein VI; ICln, chloride channel regulatory protein; IP3, inositol trisphosphate; ITAM, immunoreceptor tyrosine-based activation motif; LAT, linker for activation of T cells; LIMBS, ligand-associated metal-binding site; MIDAS, metal-ion dependent adhesion site; PAR, protease-activated receptor; PH domain, pleckstrin homology domain; PI3K, phosphatidylinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PKA, protein kinase A; PKC, protein kinase C; PLCβ(γ-2),Phospholipase Cβ(γ-2); PP1, protein phosphatase 1; RASA3, Ras GTPase-activating protein 3; RIAM, Rap1–GTP-interacting adapter molecule; SFK, Src family kinases; SH-2, Src homology 2 domain; Syk, Spleen tyrosine kinase; TRAP, thrombin receptor-activating peptide; VWF, von Willebrand factor.

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Kaneva, V.N., Martyanov, A.A., Morozova, D.S. et al. Platelet Integrin αIIbβ3: Mechanisms of Activation and Clustering; Involvement into the Formation of the Thrombus Heterogeneous Structure. Biochem. Moscow Suppl. Ser. A 13, 97–110 (2019). https://doi.org/10.1134/S1990747819010033

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