Unlocking Platelet Mechanisms through Multi-omics Integration: A Brief Review

Figures

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  Fig. (1). Platelet Signaling Regulated by Posttranslational Modifications (PTMs) [14]: Platelet activation and inhibition are controlled by alterations in PTMs, specifically glycosylation and phosphorylation. When platelets adhere to a damaged vessel wall, they transition from a discoidal to a semi round shape with filopodia. Upon exposure to agonists such as collagen and thrombin, activated platelets with filopodia release autocoids such as ADP and thromboxane. Within the cell cytosol, numerous protein kinases and phosphatases become active, initiating phosphorylation and dephosphorylation events on their target proteins. Additionally, depending on the state of platelet activation, proteases are activated and cleave their protein substrates. Moreover, modifications to platelet lipids and glycan composition play a role in the mechanisms of platelet activation (The figure was created by the Biorender tool).

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  Fig. (2). Protease detection [17, 19]: (A) Many proteases are initially found in an inactive form called zymogens. They become active through processes such as proteolysis or changes in their shape. Posttranslational modifications (PTMs) and natural inhibitors can influence the active forms of these proteases. Furthermore, active proteases are often regulated or broken down. (B) Chemical probes designed to study protease activity typically comprise three components: (1) an electrophilic compound that reacts with the active site's nucleophilic group (found in serine, cysteine, or threonine proteases), (2) a selectivity element, often a peptide that mimics the substrate preferences of the target protease, and (3) a detection tag. This detection tag may take various forms, such as a fluorescent marker for microscopic observation, biotin for purification, a radioactive isotope for imaging, or a bioorthogonal handle such as an alkyne or azide. (The figure was created by the Biorender tool).

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  Fig. (3). Overview of PTMs in the Phosphorylation Process [30]: Phosphorylation, a prevalent posttranslational modification (PTM), entails the addition of phosphate groups to proteins, imparting regulatory control by inducing changes in their conformation or interactions. This ubiquitous modification significantly impacts diverse cellular processes, including signal transduction and gene expression, underscoring its pivotal role in orchestrating intricate cellular responses. (The figure was created by the Biorender tool).

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  Fig. (4). Activation of the PKA (protein kinase-A) pathway [37, 38]: Elevated cAMP levels, resulting from a surge in intracellular signaling, stimulate PKA, a critical regulator of cellular responses. Upon activation, PKA initiates a dynamic cascade of downstream signaling events orchestrating intricate cellular processes. This pathway plays a pivotal role in mediating responses to extracellular signals and modulating various cellular functions, ultimately contributing to the regulation of physiological and biochemical activities within the cell. (The figure was created by the Biorender tool).