A computational model of PKD and CERT interactions at the trans-Golgi network of mammalian cells

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• 作者：Patrick Weber ; Mariana Hornjik ; Monilola A Olayioye…
• 关键词：Computational model ; PKD ; CERT ; Bayesian inference ; Trans ; golgi network
• 刊名：BMC Systems Biology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：9
• 期：1
• 全文大小：1,951 KB
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• 刊物主题：Bioinformatics; Systems Biology; Simulation and Modeling; Computational Biology/Bioinformatics; Physiological, Cellular and Medical Topics; Algorithms;
• 出版者：BioMed Central
• ISSN：1752-0509

文摘

Background In mammalian cells protein-lipid interactions at the trans-Golgi network (TGN) determine the formation of vesicles, which transfer secretory proteins to the cellular membrane. This process is regulated by a complex molecular network including protein kinase D (PKD), which is directly involved in the fission of transport vesicles, and its interaction with the ceramide transfer protein CERT that transports ceramide from the endoplasmic reticulum to the TGN. Results Here we present a novel quantitative kinetic model for the interactions of the key players PKD, phosphatidylinositol 4-kinase III beta (PI4KIII β) and CERT at the TGN membranes. We use sampling-based Bayesian analysis and perturbation experiments for model calibration and validation. Conclusions Our quantitative predictions of absolute molecular concentrations and reaction fluxes have major biological implications: Model comparison provides evidence that PKD and CERT interact in a cooperative manner to regulate ceramide transfer. Furthermore, we identify active PKD to be the dominant regulator of the network, especially of CERT-mediated ceramide transfer.