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

作者：Weber Patrick; Hornjik Mariana; Olayioye Monilola A; Hausser Angelika; Radde Nicole E^*

来源：BMC Systems Biology, 2015, 9(1): UNSP 9.

DOI：10.1186/s12918-015-0147-1

• Computational model
• PKD
• CERT
• Bayesian inference
• Trans-golgi network

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 beta) 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.

• 出版日期2015-2-26