Mechanisms of receptor shedding in platelets

Abstract

The ability to upregulate and downregulate surface-exposed proteins and receptors is a powerful process that allows a cell to instantly respond to its microenvironment. In particular, mobile cells in the bloodstream must rapidly react to conditions where infection or inflammation are detected, and become proadhesive, phagocytic, and/or procoagulant. Platelets are one such blood cell that must rapidly acquire and manage proadhesive and procoagulant properties in order to execute their primary function in hemostasis. The regulation of platelet membrane properties is achieved via several mechanisms, one of which involves the controlled metalloproteolytic release of adhesion receptors and other proteins from the platelet surface. Proteolysis effectively lowers receptor density and reduces the reactivity of platelets, and is a mechanism to control robust platelet activation. Recent research has also established clear links between levels of platelet receptors and platelet lifespan. In this review, we will discuss the current knowledge of metalloproteolytic receptor regulation in the vasculature with emphasis on the platelet receptor system to highlight how receptor density can influence both platelet function and platelet survival.

Metal–Organic‐Framework‐Derived Carbon Nanostructures for Site‐Specific Dual‐Modality Photothermal/Photodynamic Thrombus Therapy

“…Therefore, as shown in Figure a, platelets were assessed by flow cytometry with the assistance of fluorescein isothiocyanate‐CD41 (FITC‐CD41) for predicting whether the PSs would trigger platelets activation. Platelets activated with adenosine diphosphate (ADP) were adopted as a positive control . Conversely, platelets without any treatment were explored as a negative control.…”

Imaging Platelet Processes and Function—Current and Emerging Approaches for Imaging in vitro and in vivo

“…An additional consequence of receptor activation is the metalloproteolytic shedding of the ligand-binding ectodomains of GPIbα (the ligand-binding portion of GPIb-IX-V) and GPVI receptors. Through this metalloproteolytic process, thrombus propagation may be controlled and limited (34,35). FIGURE 1 | Platelet contributions to thrombus formation.…”

Modulation of Immune Responses by Platelet-Derived ADAM10

“…The activity of (p)ADAM10 is highly regulated on multiple levels including transcription, translation and posttranslation [reviewed in (108,134,135)] Once translated, full-length ADAM10 trafficks through the secretory pathway where it is activated by removal of its prodomain (136). Substrate-access to the catalytic site of mature ADAM10 is still tightly regulated through conformational changes involving its cysteine-rich domain (137).…”

“…ADAM10 activity might additionally be modulated by the dynamic composition of the lipid-bilayer by mechanisms such as trapping of substrates within cholesterin-rich lipid-rafts which are usually devoid of ADAM10 [reviewed in (141)]. Moreover, Ca 2+ and calmodulin are important regulators of ADAM10 activity (142) also in platelets (135). It was suggested that pro-ADAM10 associates with calmodulin and that Ca 2+ influx allows ADAM10-maturation by disrupting this association (56).…”