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首页> 外文期刊>Current Biology: CB >Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment
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Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment

机译：囊泡交通建模揭示了Cdc42p介导的极性建立的意外后果。

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Background: Polarization in yeast has been proposed to involve a positive feedback loop whereby the polarity regulator Cdc42p orients actin cables, which deliver vesicles carrying Cdc42p to the polarization site. Previous mathematical models treating Cdc42p traffic as a membrane-free flux suggested that directed traffic would polarize Cdc42p, but it remained unclear whether Cdc42p would become polarized without the membrane-free simplifying assumption. Results: We present mathematical models that explicitly consider stochastic vesicle traffic via exocytosis and endocytosis, providing several new insights. Our findings suggest that endocytic cargo influences the timing of vesicle internalization in yeast. Moreover, our models provide quantitative support for the view that integral membrane cargo proteins would become polarized by directed vesicle traffic given the experimentally determined rates of vesicle traffic and diffusion. However, such traffic cannot effectively polarize the more rapidly diffusing Cdc42p in the model without making additional assumptions that seem implausible and lack experimental support. Conclusions: Our findings suggest that actin-directed vesicle traffic would perturb, rather than reinforce, polarization in yeast. Highlights: New strategy for mathematical modeling of Cdc42p traffic explicitly considers vesicles Vesicular traffic can polarize v-SNAREs but not Cdc42p The plausibility of the Cdc42p-actin-vesicle positive feedback loop is in question Endocytic cargo can influence coated-pit internalization in yeast
机译：背景：已提出酵母中的极化涉及正反馈回路，由此极性调节剂Cdc42p定向肌动蛋白电缆，从而将携带Cdc42p的囊泡输送至极化位点。以前将Cdc42p流量视为无膜通量的数学模型表明，定向流量会使Cdc42p极化，但尚不清楚如果没有无膜简化假设，Cdc42p是否会极化。结果：我们提出了数学模型，该模型明确地考虑了通过胞吐作用和胞吞作用的随机囊泡运输，提供了一些新的见解。我们的发现表明内吞货物影响酵母中囊泡内在化的时间。此外，我们的模型为以下观点提供了定量支持：鉴于实验确定的囊泡运输和扩散速率，整合膜货物蛋白将被定向的囊泡运输极化。但是，这种流量无法有效地极化模型中扩散较快的Cdc42p，而无需做出似乎难以置信且缺乏实验支持的其他假设。结论：我们的发现表明，肌动蛋白定向的囊泡运输将干扰而不是加强酵母中的极化。亮点：对Cdc42p流量进行数学建模的新策略明确考虑了囊泡囊泡流量可以极化v-SNARE，但不能极化Cdc42p。Cdc42p-肌动蛋白-囊泡正反馈回路的合理性尚有疑问

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