Discrete, continuous, and stochastic models of protein sorting in the Golgi apparatus

Abstract

The Golgi apparatus plays a central role in processing and sorting proteins and lipids in eukaryotic cells. Golgi compartments constantly exchange material with each other and with other cellular components, allowing them to maintain and reform distinct identities despite dramatic changes in structure and size during cell division, development, and osmotic stress. We have developed three minimal models of membrane and protein exchange in the Golgi—a discrete, stochastic model, a continuous ordinary differential equation model, and a continuous stochastic differential equation model—each based on two fundamental mechanisms: vesicle-coat-mediated selective concentration of cargoes and soluble N-ethylmaleimide-sensitive factor attachment protein receptor SNARE proteins during vesicle formation and SNARE-mediated selective fusion of vesicles. By exploring where the models differ, we hope to discover whether the discrete, stochastic nature of vesicle-mediated transport is likely to have appreciable functional consequences for the Golgi. All three models show similar ability to restore and maintain distinct identities over broad parameter ranges. They diverge, however, in conditions corresponding to collapse and reassembly of the Golgi. The results suggest that a continuum model provides a good description of Golgi maintenance but that considering the discrete nature of vesicle-based traffic is important to understanding assembly and disassembly of the Golgi. Experimental analysis validates a prediction of the models that altering guanine nucleotide exchange factor expression levels will modulate Golgi size.

Computational analysis of the roles of ER-Golgi network in the cell cycle

“…ATF6 is an ubiquitously expressed ER transmembrane protein. In response to ER stress or abnormal accumulation of misfolded proteins on the ER, ATF6 will be transported to the Golgi apparatus through its interaction with the coat protein II (COPII) complex [ 1 ], which is regulated by the GEF and tSNARE mechanism validated in our previous Golgi research [ 7 , 8 ]. The site 1 protease (S1P) and S2P in the Golgi apparatus will process ATF6 and release its N-terminal cytosolic domain fragment (ATF6f) to the cytoplasm.…”

“…Our previous work [ 7 , 8 ] based on discrete stochastic simulation methods found that, changing the expression level of GEF and tSNARE proteins in the ER-Golgi network could modulate the size of Golgi apparatus. Moreover, Golgi's function and size undergo dramatic changes during the development of several diseases [ 2 ].…”

From cartoons to quantitative models in Golgi transport

“…It is clear that our approach is not the first mathematical model implemented to represent the Golgi structure and the transport of cargoes ( Gong et al, 2010). Several research groups have published different models addressing organelle self-organization and protein and lipid sorting in the Golgi (for a review, see .…”

Golgi Glycosylation and Human Inherited Diseases

“…Recent proposed explanations for the organization, dynamics, and flux of both proteins and lipids through the Golgi are based primarily on their physical properties, and sites of synthesis/depletion to construct membranes of different compositions, dimensions, and curvatures (Lippincott-Schwartz and Phair 2010). Lipid and protein sorting are interwoven and interdependent in this attractive, but unproven model (Emr et al 2009;Gong et al 2010). However, it provides a setting to discuss the possibility that altered glycosylation may be a useful marker or play a role in pathophysiology of the disorders.…”