Navigation through the Plasma Membrane Molecular Landscape Shapes Random Organelle Movement.
Navigation through the Plasma Membrane Molecular Landscape Shapes Random Organelle Movement.
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DOI：
10.1016/j.cub.2016.12.002
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发表时间：
2017-02-06
期刊：
影响因子：
--
通讯作者：
Duncan RR
中科院分区：
文献类型：
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作者：
Dun AR;Lord GJ;Wilson RS;Kavanagh DM;Cialowicz KI;Sugita S;Park S;Yang L;Smyth AM;Papadopulos A;Rickman C;Duncan RR
真核细胞质膜组织理论长期以来一直存在争议，部分原因是缺乏合适的高分辨率技术来原位探测分子结构和整合来自不同数据流的信息。值得注意的是，膜蛋白的簇状模式在不同的蛋白家族中是一个普遍保守的特征(参见)，包括SNARS、SM蛋白、离子通道和受体(例如)。人们在分析分泌细胞器的行为方面做了大量的工作，而理解细胞膜和近端细胞器之间的关系是细胞生物学的一个基本目标，因为可能会建立广泛的概念或规则。在这里，我们探索了被普遍接受的模型，即质膜上的小泡由细胞骨架轨迹引导到膜上的特定位置，这些位置具有聚集的分泌分子机制，部分由局部脂质组成组织。为了增加我们对这些基本过程的理解，我们将分泌机制的纳米显微镜和光谱学与细胞器跟踪数据整合在一个数学模型中，用击倒细胞模型迭代。我们发现，连续囊泡的重复路线，相似融合位点的重复使用，以及明显不同的囊泡“池”，都是由覆盖在质膜上的非反应性分泌蛋白分子库之间导航的细胞器的布朗行为形成的。膜-近端囊泡运动是质膜上的随机分泌分子，组织成构象簇，随机囊泡运动在这些簇之间导航，该模型解释了囊泡的行为，而不需要功能池Dun等人。使用数学建模、超分辨率成像和生物扰动来塑造膜分子景观，检查质膜和细胞器动力学之间的相互关系。它们表明，细胞表面的分泌囊泡随机移动，在分泌机械分子储存库之间导航。
Eukaryotic plasma membrane organization theory has long been controversial, in part due to a dearth of suitably high-resolution techniques to probe molecular architecture in situ and integrate information from diverse data streams. Notably, clustered patterning of membrane proteins is a commonly conserved feature across diverse protein families (reviewed in), including the SNAREs, SM proteins, ion channels, and receptors (e.g.,). Much effort has gone into analyzing the behavior of secretory organelles, and understanding the relationship between the membrane and proximal organelles is an essential goal for cell biology as broad concepts or rules may be established. Here we explore the generally accepted model that vesicles at the plasmalemma are guided by cytoskeletal tracks to specific sites on the membrane that have clustered molecular machinery for secretion, organized in part by the local lipid composition. To increase our understanding of these fundamental processes, we integrated nanoscopy and spectroscopy of the secretory machinery with organelle tracking data in a mathematical model, iterating with knockdown cell models. We find that repeated routes followed by successive vesicles, the re-use of similar fusion sites, and the apparently distinct vesicle “pools” are all fashioned by the Brownian behavior of organelles overlaid on navigation between non-reactive secretory protein molecular depots patterned at the plasma membrane. Membrane-proximal vesicle movements are random Secretory molecules at the plasma membrane organize into conformational clusters Random vesicle movements navigate among these clusters This model explains vesicle behaviors without a requirement for functional pools Dun et al. use mathematical modeling, super-resolution imaging, and biological perturbations to shape the membrane molecular landscape, examining the inter-relationship between the plasma membrane and organelle dynamics. They show that secretory vesicles at the cell surface move randomly, navigating among depots of secretory machinery molecules.