Accommodation of large cargo within Golgi cisternae

 描述（由申请人提供）：高尔基复合体是一种普遍存在的真核细胞器，在新合成的蛋白质和脂质的翻译后加工和分选中发挥核心作用。高尔基复合体的这两种功能都是至关重要的，因为加工和靶向的缺陷可能导致疾病。在哺乳动物细胞中，高尔基复合体有一种不寻常的结构，由一组堆叠的池膜组成，在细胞核附近聚集成一条带状。这种复杂结构的功能尚不清楚，但它可能有助于货物的有效处理和分类。高尔基体的结构可以迅速和可逆地改变在货物的通道。在转运大型货物如脂蛋白颗粒、前胶原束和出芽进入细胞内区室的包膜病毒期间，结构变化特别显著。高尔基复合体发生可逆形态学变化以容纳大货物的机制尚未得到实验解决。拟议的实验将测试的假设，在高尔基体的大型货物的到来激活信号通路，导致池扩张和有效的高尔基体内运输。该项目的具体目标是：（1）以冠状病毒为模型，确定高尔基体如何被修饰以容纳和运输大的包膜病毒颗粒;（2）比较和对比肠上皮细胞产生的乳糜微粒以及可以在分泌途径中的各个点分期的合成大货物所使用的机制。这些研究将为高尔基体结构和功能的未研究方面提供新的信息，并导致对疾病中被破坏的正常细胞过程的深入了解。

 DESCRIPTION (provided by applicant): The Golgi complex is a ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids. Both of these functions of the Golgi complex are critical, since defects in processing and targeting can lead to disease. In mammalian cells, the Golgi complex has an unusual structure consisting of sets of stacked cisternal membranes gathered into a ribbon near the nucleus. The function of this elaborate structure is unknown, but it may contribute to efficient processing and sorting of cargo. Golgi structure can be rapidly and reversibly altered during passage of cargo. The structural alterations are particularly dramatic during transport of large cargo such as lipoprotein particles, procollagen bundles, and enveloped viruses that bud into intracellular compartments. The mechanism by which the Golgi complex undergoes reversible morphological changes to accommodate large cargo has not been experimentally addressed. The proposed experiments will test the hypothesis that arrival of large cargo at the Golgi activates signaling pathways that result in cisternal dilation and efficient intra-Golgi transport. The specific aims of the project are to: (1) determine how the Golgi is modified to accommodate and transport large enveloped virus particles, using coronavirus as a model; and (2) compare and contrast the mechanism used by chylomicrons produced by intestinal epithelial cells as well as a synthetic large cargo that can be staged at various points in the secretory pathway. These studies will provide novel information on unstudied aspects of Golgi structure and function, and lead to insights into normal cellular processes that are disrupted in disease.