Contribution of the endoplasmic reticulum to peroxisome formation

Contribution of the endoplasmic reticulum to peroxisome formation
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DOI:
10.1016/j.cell.2005.04.025
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发表时间:
2005-07-15
期刊:
影响因子:
64.5
通讯作者:
Tabak, HF
Tabak, HF
中科院分区:
生物学1区
文献类型:
--
作者:
Hoepfner, D;Schildknegt, D;Tabak, HF

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真核细胞中的过氧化物体是如何形成的尚不清楚,但对于深入了解各种疾病很重要。由于PEX3或PEX19基因突变而缺乏过氧化体的人类和酵母细胞,在重新引入相应的野生型版本后,都会再生细胞器。为了评估新的过氧化物体是如何形成的以及从哪里形成的,我们用实时荧光显微镜跟踪了新合成的YFP标记的Pex3和Pex19蛋白在酿酒酵母中的运输路线。值得注意的是,Pex3(一种完整的膜蛋白)首先可以在内质网(ER)中观察到,它集中在病灶中,然后以依赖于Pex19的方式发芽,成熟为功能齐全的过氧体。Pex19(一种法尼化的,主要是胞浆的蛋白)首先在内质网上的Pex3处富含,然后在成熟的过氧体上富含。Pex3-YFP的这种转运途径在野生型细胞中是相同的。这些结果表明,过氧化体是从内质网中的结构域产生的。
How peroxisomes are formed in eukaryotic cells is unknown but important for insight into a variety of diseases. Both human and yeast cells lacking peroxisomes due to mutations in PEX3 or PEX19 genes regenerate the organelles upon reintroduction of the corresponding wild-type version. To evaluate how and from where new peroxisomes are formed, we followed the trafficking route of newly made YFP-tagged Pex3 and Pex19 proteins by real-time fluorescence microscopy in Saccharomyces cerevisiae. Remarkably, Pex3 (an integral membrane protein) could first be observed in the endoplasmic reticulum (ER), where it concentrates in foci that then bud off in a Pex19-dependent manner and mature into fully functional peroxisomes. Pex19 (a farnesylated, mostly cytosolic protein) enriches first at the Pex3 foci on the ER and then on the maturing peroxisomes. This trafficking route of Pex3-YFP is the same in wild-type cells. These results demonstrate that peroxisomes are generated from domains in the ER.