BIOPHYSICAL THEORY AND MODELING |
Simulated de novo assembly of Golgi compartments by selective cargo capture during vesicle budding and targeted vesicle fusion
Haijun Gong 1, Debrup Sengupta 1, Adam D. Linstedt 1 and Russell Schwartz 1*
1 Carnegie Mellon University
* To whom correspondence should be addressed. E-mail: russells{at}andrew.cmu.edu.
Submitted on December 11, 2007
Revised on January 13, 2008
Accepted on 18 April 2008
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Abstract |
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The Golgi apparatus is comprised of stacked cisternal membranes forming subcompartments specialized for post-translational processing of newly synthesized secretory cargo. Recent experimental evidence indicates that the Golgi apparatus can undergo de novo biogenesis from the endoplasmic reticulum but the mechanism by which the membranes self assemble into compartmentalized structures remains unknown. We developed a discrete-event computer simulation model to test whether two fundamental mechanisms- vesicle coat mediated selective concentration of SNARE proteins during vesicle formation and SNARE-mediated selective fusion of vesicles- suffice to generate and maintain compartments. Simulations verified that this minimal model is adequate for homeostasis of pre-established compartments, even in response to small perturbations, and for de novo formation of stable compartments. The model led to a novel prediction that Golgi size is, in part, dependent on target SNARE expression level. This prediction was supported by a demonstration that exogenous expression of the Golgi target SNARE syntaxin-5 alters Golgi size in living cells.
Key Words:
coarse-grained model, discrete event simulation, membrane sorting, stochastic simulation algorithm, trafficking, vesicular transport
