Dataset Information

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation.

ABSTRACT:

Background

Accurate protein quantification is a vital prerequisite for generating meaningful predictions when using systems biology approaches, a method that is increasingly being used to unravel the complexities of subcellular interactions and as part of the drug discovery process. Quantitative proteomics, flow cytometry, and western blotting have been extensively used to define human platelet protein copy numbers, yet for mouse platelets, a model widely used for platelet research, evidence is largely limited to a single proteomic dataset in which the total amount of proteins was generally comparatively higher than those found in human platelets.

Objectives

To investigate the functional implications of discrepancies between levels of mouse and human proteins in the glycoprotein VI (GPVI) signalling pathway using a systems pharmacology model of GPVI.

Methods

The protein copy number of mouse platelet receptors was determined using flow cytometry. The Virtual Platelet, a mathematical model of GPVI signalling, was used to determine the consequences of protein copy number differences observed between human and mouse platelets.

Results and conclusion

Despite the small size of mouse platelets compared to human platelets they possessed a greater density of surface receptors alongside a higher concentration of intracellular signalling proteins. Surprisingly the predicted temporal profile of Syk activity was similar in both species with predictions supported experimentally. Super resolution microscopy demonstrates that the spatial distribution of Syk is similar between species, suggesting that the spatial distribution of receptors and signalling molecules in activated platelets, rather than their copy number, is important for signalling pathway regulation.

SUBMITTER: Dunster JL

PROVIDER: S-EPMC7027541 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation.

Dunster Joanne L JL Unsworth Amanda J AJ Bye Alexander P AP Haining Elizabeth J EJ Sowa Marcin A MA Di Ying Y Sage Tanya T Pallini Chiara C Pike Jeremy A JA Hardy Alexander T AT Nieswandt Bernhard B García Ángel Á Watson Steve P SP Poulter Natalie S NS Gibbins Jonathan M JM Pollitt Alice Y AY

Journal of thrombosis and haemostasis : JTH 20191206 2

<h4>Background</h4>Accurate protein quantification is a vital prerequisite for generating meaningful predictions when using systems biology approaches, a method that is increasingly being used to unravel the complexities of subcellular interactions and as part of the drug discovery process. Quantitative proteomics, flow cytometry, and western blotting have been extensively used to define human platelet protein copy numbers, yet for mouse platelets, a model widely used for platelet research, evid ...[more]

PMID: 31680418

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Dataset Information

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation.

Background

Objectives

Methods

Results and conclusion

Publications

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation.

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