title: A computational model of PKD and CERT interactions at the trans-Golgi network of mammalian cells.
abstract: 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.
authors.affiliation: Institute for Systems Theory and Automatic Control, University of Stuttgart, Pfaffenwaldring 9, Stuttgart, 70569, Germany. patrick.weber@ist.uni-stuttgart.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weber
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, 70569, Germany. m.hornjik1976@gmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Hornjik
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, 70569, Germany. monilola.olayioye@izi.uni-stuttgart.de.
authors.forename: Monilola A
authors.initials: MA
authors.lastname: Olayioye
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, 70569, Germany. izbhauss@izi.uni-stuttgart.de.
authors.forename: Angelika
authors.initials: A
authors.lastname: Hausser
authors.affiliation: Institute for Systems Theory and Automatic Control, University of Stuttgart, Pfaffenwaldring 9, Stuttgart, 70569, Germany. nicole.radde@ist.uni-stuttgart.de.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Radde
mesh_terms: D001499:Bayes Theorem; D001692:Biological Transport; D002138:Calibration; D002352:Carrier Proteins / Q000378:metabolism*; D002518:Ceramides / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D002518:Ceramides; C089212:protein kinase D; D011493:Protein Kinase C