A comprehensive kinetic model of the exocytotic process: Evaluation of the reaction mechanism

This study presents a comprehensive, quantitative description of the exocytotic process that has both analytic and predictive powers. The model utilizes strict chemical formalism and is based on a set of equilibria between the various SNARE proteins, their complexes and the reaction which free Ca2+ ions. All these reactions are linked by first and second order rate constants. With the proper set of rate constants, which were selected by a systematic search in a multi dimensional parameter space, the model reconstructs the fusion dynamics as recorded under divergent experimental protocols: the effect of repeated depolarization, recovery after depletion of the vesicular pools of the cell, and over-expression or knockout of specific proteins. The model provides a detailed scenario of the maturation process, where the vesicles progress from the early steps of the SNARE complex formation up to the last event of the vesicles' fusion with the cells' plasma membrane. The dynamics of each intermediate enable us to describe the experimental result in terms of overall flow, where upstream intermediates are mobilized during the progression of the reaction.