Abstract Number: PB0846
Meeting: ISTH 2022 Congress
Background: Platelets express junction proteins that are known to regulate cell-cell adhesion, barrier formation and communication in tissue forming cells. Previous research has shown that the gap junction proteins expressed by platelets regulate platelet activation in an αIIbβ3-dependent manner. Also, platelet activation processes are negatively regulated by endothelial cell-selective adhesion molecule (ESAM) and junctional adhesion molecule A (JAM-A), proteins that are part of the tight junctions (TJ) of endothelial cells. However, the role of zonula occludens 2 (ZO-2) -an intracellular component of the endothelial TJs- in the formation of inter-platelet contacts has not yet been described.
Aims: To unravel the molecular composition, in particular ZO-2, of tight platelet-platelet contacts.
Methods: Using phosphoproteomics databases, ZO-2 phosphorylation in activated platelets was investigated. Isolated platelets were allowed to fully spread on a fibrinogen surface. Fixed samples were stained to assess F-actin polymerization in relation to ZO-2 and ESAM distribution using confocal and/or super-resolution fluorescence microscopy. Platinum replica electron microscopy was applied for ultrastructural visualization of the cytoskeleton at sites of platelet-platelet interaction.
Results: ZO-2 undergoes extensive phosphorylation changes upon agonist-induced platelet activation as well as cAMP-mediated platelet inhibition. Confocal and super-resolution fluorescence microscopy indicated a marked redistribution and clustering of ZO-2 molecules at sites of platelet-platelet contacts, in which ZO-2 colocalized with ESAM. Furthermore, platinum replica electron microscopy revealed that inter-platelet contacts resulted in the merging of the circumferential actin bundles between interacting platelets. These phenomena were antagonized by cAMP elevation.
Conclusion(s): Jointly, these data point to the assembly of tight junction-like structures, where intracellular components of tight junctions accumulate at sites of close platelet-platelet contact.
This work was supported by the Dutch Heart Foundation (2020T020 to C.B.)
To cite this abstract in AMA style:Nagy M, Bender M, Poulter N, Sickmann A, Stéphenne X, Brouns S, Koenen R, ten Cate H, Heemskerk J, Baaten C. ZO-2 Enriched Tight Junction-like Structures at Sites of Platelet-Platelet Contact [abstract]. https://abstracts.isth.org/abstract/zo-2-enriched-tight-junction-like-structures-at-sites-of-platelet-platelet-contact/. Accessed February 27, 2024.
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