Deciphering the Roles of N-Glycans on Collagen–Platelet Interactions

Toonstra, Christian; Hu, Yingwei; Zhang, Hui

doi:10.1021/acs.jproteome.9b00003

Cited by 15 publications

(12 citation statements)

References 61 publications

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“…Another study detected 0.8 k extra-cytosolic N-linked glycosylation sites with some of these regulated by GPVI [63]. This agrees with the finding that glycan glycosylation plays a role in plateletcollagen interaction [64]. In GPVI-stimulated platelets, it appeared that 0.9 k out of 1.6 k ubiquitinylated peptides (corresponding to 0.7 k proteins, including Syk, filamin and integrins) were upregulated, implicating a profound role of GPVI in the ubiquitin protein degradation pathway [65].…”

Section: Collagen Receptor Glycoprotein VI (Gpvi)supporting

confidence: 82%

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

Huang

Zhang

Solari

et al. 2021

IJMS

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Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles are tightly regulated by a complex network of signalling pathways. Mass spectrometry-based proteomic techniques are contributing not only to the identification and quantification of new platelet proteins, but also reveal post-translational modifications of these molecules, such as acetylation, glycosylation and phosphorylation. Moreover, target proteomic analysis of platelets can provide molecular biomarkers for genetic aberrations with established or non-established links to platelet dysfunctions. In this report, we review 67 reports regarding platelet proteomic analysis and signalling on a molecular base. Collectively, these provide detailed insight into the: (i) technical developments and limitations of the assessment of platelet (sub)proteomes; (ii) molecular protein changes upon ageing of platelets; (iii) complexity of platelet signalling pathways and functions in response to collagen, rhodocytin, thrombin, thromboxane A2 and ADP; (iv) proteomic effects of endothelial-derived mediators such as prostacyclin and the anti-platelet drug aspirin; and (v) molecular protein changes in platelets from patients with congenital disorders or cardiovascular disease. However, sample sizes are still low and the roles of differentially expressed proteins are often unknown. Based on the practical and technical possibilities and limitations, we provide a perspective for further improvements of the platelet proteomic field.

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Section: Collagen Receptor Glycoprotein VI (Gpvi)supporting

confidence: 82%

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

Huang

Zhang

Solari

et al. 2021

IJMS

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“…Further supporting our results, the treatment of platelets with neuraminidase reduced their aggregation induced by ADP [ 27 ]. Moreover, abnormalities in the N-glycosylation of GPVI could contribute to acquired defects in GPVI-mediated platelet reactivity to collagen [ 8 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The function of platelet receptors that mediate their adhesive and aggregative properties are strongly reliant upon N-glycosylation to modulate the orientation of glycoproteins to facilitate interaction between proteins [ 29 ]. A mutational study performed on β3 demonstrated that loss of N-glycoside sites impaired either αIIbβ3 expression or function.…”

Section: Discussionmentioning

confidence: 99%

The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia

Ramírez-López

Roman

Manzano

et al. 2021

JCM

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Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocytopaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count <30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and activate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets’ surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity.

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“…Under the high shear conditions, the GPIb-V-IX receptor complex is required to stabilize platelet adhesion to the vessel surface, besides collagen receptor glycoprotein (GP) VI and αIIbβ3 integrin, which indirectly interact with collagen via VWF [ 16 ]. Recent proteomics studies describe both the positive and negative influences of N-glycosylation on collagen-platelets interactions [ 17 ]. At low shear conditions, the binding to collagen via α2β1 integrin has a major role in platelet adhesion to the injured endothelium.…”

Section: Platelets Biology and Functionsmentioning

confidence: 99%

Proteomics: A Tool to Study Platelet Function

Shevchuk

Begonja

Gambaryan

et al. 2021

IJMS

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Platelets are components of the blood that are highly reactive, and they quickly respond to multiple physiological and pathophysiological processes. In the last decade, it became clear that platelets are the key components of circulation, linking hemostasis, innate, and acquired immunity. Protein composition, localization, and activity are crucial for platelet function and regulation. The current state of mass spectrometry-based proteomics has tremendous potential to identify and quantify thousands of proteins from a minimal amount of material, unravel multiple post-translational modifications, and monitor platelet activity during drug treatments. This review focuses on the role of proteomics in understanding the molecular basics of the classical and newly emerging functions of platelets. including the recently described role of platelets in immunology and the development of COVID-19.The state-of-the-art proteomic technologies and their application in studying platelet biogenesis, signaling, and storage are described, and the potential of newly appeared trapped ion mobility spectrometry (TIMS) is highlighted. Additionally, implementing proteomic methods in platelet transfusion medicine, and as a diagnostic and prognostic tool, is discussed.

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Deciphering the Roles of N-Glycans on Collagen–Platelet Interactions

Cited by 15 publications

References 61 publications

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia

Proteomics: A Tool to Study Platelet Function

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