School of Mathematics & Physics, The University of Queensland, Brisbane, Australia.
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute (QBI), The University of Queensland, Brisbane, Australia.
PLoS One. 2022 Mar 16;17(3):e0264521. doi: 10.1371/journal.pone.0264521. eCollection 2022.
Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane.
通过整合细胞内标记神经分泌小泡运输的成像分析结果，我们开发了一个马尔可夫状态模型来描述它们的运输和结合动力学。我们的模拟结果表明，在刺激物刺激下，神经分泌小泡会发生空间再分布，导致小泡向质膜移动，在那里它们发生融合，从而释放肾上腺素和去甲肾上腺素。此外，我们发现这种再分布本身就可以解释在刺激下观察到的囊泡运输的上调及其对质膜的定向偏倚。参数拟合表明，在细胞内较深的隔室中，囊泡运输是不对称的，表现出向质膜的偏向。
