Cargo loading at the ER
Cargo loading at the ER
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DOI：
10.3109/09687688.2010.506203
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发表时间：
2010-11
影响因子：
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通讯作者：
Katy Schmidt;D. Stephens
中科院分区：
文献类型：
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作者：
Katy Schmidt;D. Stephens
通过早期分泌途径运输新合成的货物定义并维持真核细胞的细胞内组织以及组织和器官的组织。这一途径的重要性是强调了越来越多的突变的关键组成部分的ER输出机制，是人类疾病的多样性的原因。在这里，我们讨论的分子机制，决定货物选择在囊泡出芽。虽然，在体外重建测定，单细胞生物体，如芽殖酵母，和哺乳动物细胞培养物仍然有很多提供在获得分泌货物出口的分子基础的充分理解方面，这样的测定到目前为止已被限制在较小的，自由扩散的货物的分析。大分子复合物如胶原蛋白（高达300 nm）或脂蛋白（约500 nm）从ER的输出在保持输出的选择性和效率方面存在明显的问题。同样清楚的是，为了将我们对ER输出的分子基础的知识转化为对正常发育和疾病进展的充分理解，使用后生动物模型是必不可少的。结合起来，这些方法现在不仅开始阐明ER大分子货物出口的机制，而且还揭示了这一过程失败对人类发育和疾病的影响。
Abstract Trafficking of newly synthesized cargo through the early secretory pathway defines and maintains the intracellular organization of eukaryotic cells as well as the organization of tissues and organs. The importance of this pathway is underlined by the increasing number of mutations in key components of the ER export machinery that are causative of a diversity of human diseases. Here we discuss the molecular mechanisms that dictate cargo selection during vesicle budding. While, in vitro reconstitution assays, unicellular organisms such as budding yeast, and mammalian cell culture still have much to offer in terms of gaining a full understanding of the molecular basis for secretory cargo export, such assays have to date been limited to analysis of smaller, freely diffusible cargoes. The export of large macromolecular complexes from the ER such as collagens (up to 300 nm) or lipoproteins (∼500 nm) presents a clear problem in terms of maintaining both selectivity and efficiency of export. It has also become clear that in order to translate our knowledge of the molecular basis for ER export to a full understanding of the implications for normal development and disease progression, the use of metazoan models is essential. Combined, these approaches are now starting to shed light not only on the mechanisms of macromolecular cargo export from the ER but also reveal the implications of failure of this process to human development and disease.