Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.
PLoS Biol. 2009 Sep;7(9):e1000204. doi: 10.1371/journal.pbio.1000204. Epub 2009 Sep 29.
Endocytic vesicle formation is a complex process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane. Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear. That is, how the proper temporal and spatial coordination of endocytic events is achieved and what drives vesicle scission are not known. Drawing upon detailed knowledge from experiments in yeast, we develop the first integrated mechanochemical model that quantitatively recapitulates the temporal and spatial progression of endocytic events leading to vesicle scission. The central idea is that membrane curvature is coupled to the accompanying biochemical reactions. This coupling ensures that the process is robust and culminates in an interfacial force that pinches off the vesicle. Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells. The combination of experiments and theory in this work suggest a unified mechanism for endocytic vesicle formation across eukaryotes.
内吞小泡的形成是一个复杂的过程，它将连续的蛋白质募集和脂质修饰与质膜的剧烈形状转变联系起来。尽管已经对单个分子参与者进行了深入研究，但它们如何融入内吞作用的连贯图景仍然不清楚。也就是说，如何实现内吞事件的适当时间和空间协调，以及是什么驱动了小泡的分裂，这些都还不清楚。利用来自酵母实验的详细知识，我们开发了第一个综合的机械化学模型，该模型定量地再现了导致小泡分裂的内吞事件的时间和空间进展。其核心思想是膜曲率与伴随的生化反应相耦合。这种耦合确保了该过程具有稳健性，并最终产生了一种界面力，将小泡分离。计算出的相图再现了实验中观察到的内吞突变表型，并预测了酵母和哺乳动物细胞中独特的可测试内吞表型。这项工作中的实验和理论的结合为真核生物的内吞小泡形成提供了一个统一的机制。
