Alan Nurden: Structural Complexity of Contact Sites within Platelet Aggregates
Alan Nurden, Emeritus Research Director at CNRS, Co-Founder of the French National Reference Centre for Inherited Platelet Disorders (CRPP), shared a post on LinkedIn about a recent article by Magdolna Nagy et al., published in RPTH, adding:
”This remarkable paper from Dutch researchers highlights the structural complexity of the contact sites within platelet aggregates.
While Fg and VWF bind to activated GPIIb-IIIa complexes (integrin alphaIIbbeta3) and bring platelets together into an aggregate the latter is a dynamic structure featuring an interplay between cytoskeletal structures and a family of proteins many of which are also known for their contribution to cell junctions in tissues. These include members from the claudin, connexin, ESAM and JAM families and, as now shown, tight junction protein-2 (TJP2) (also known as zonula occludens-2).
State-of-the-art electron and fluorescent microscopy showed how actin filaments modulate specific clustering of TJP2 with ESAM and JAM-A in tight lateral junctions of platelets spread on Fg and within platelet aggregates formed with a series of agonists.
Preventing their formation may be an interesting approach for antithrombotic therapy.
In view of my interests, their initial dependence on alphaIIbbeta3 should mean that they do not form in the GPVI and fibrin-dependent platelet masses that can sometimes occur in patients with the platelet-based bleeding disorder, Glanzmann thrombasthenia, where treatment of extremely rare thrombotic problems causes concern in terms of aggravating the bleeding risk. Maybe blocking GPVI could be looked at for these patients in such situations.”
Title: Formation of tight junction-like structures of zonula occludens 2 in platelet–platelet interaction
Authors: Magdolna Nagy, Markus Bender, Natalie S. Poulter, Jeremy A. Pike, Albert Sickmann, Sonja Vondenhoff, Natalia Bielicka, Marc A.M.J. van Zandvoort, Rory R. Koenen, Hugo ten Cate, Xavier Stéphenne, Johan W.M. Heemskerk, Constance C.F.M.J. Baaten
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