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Modeling protein interaction network and mechanisms in exocytosis
Wen Zhou; Tian Xia; Jiansong Tong; Dickerson, J.; Bo Su; Xun Gu;
Bioinformatics and Bioengineering, 2007. BIBE 2007. Proceedings of the 7th IEEE International Conference on
14-17 Oct. 2007
Page(s):665
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672
Abstract:
Exocytosis is an essential process in all eukaryotic cells that allows communication in cells through vesicles which contain a wide range of intracellular molecules such as hormones, matrix proteins and neurotransmitters. Recent studies have shown this process is regulated by molecular interactions among a group of well defined and conserved proteins. To gain insight into the dynamics of these interactions, we use protein interaction network modeling to investigate exocytotic system (particularly in endocrine) computationally and mathematically. The protein interactions are formulated into ordinary differential equations (ODE). We then apply a novel mathematic approach to estimate model parameters from experimental data for SNAREs-only network (with three key proteins), which is a subset of this system. Our approach is able to sense temporal changes in protein concentration and ratios of multiple proteins and precisely reconstruct the dynamical process of exocytosis, including vesicle docking, priming and fusion. Additionally, the model suggests that initial concentration of synaptic proteins plays a crucial role in efficiency of vesicle fusion, based on system stability analysis.
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