A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.

A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.
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DOI:
10.1083/jcb.201602064
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发表时间:
2016-11-21
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Prinz WA
Prinz WA
中科院分区:
其他
文献类型:
--
作者:
Joshi AS;Huang X;Choudhary V;Levine TP;Hu J;Prinz WA

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Joshi等人发现Pex30 p和Pex31 p含有网状蛋白样内质网微管结构域。像网织,他们本地化的ER片和小管的边缘,但只存在于子域。这些亚结构域是缺乏网和前过氧化物酶体囊泡生物发生的网站。酿酒酵母含有三种保守的reticulon和reticulon样蛋白,其通过稳定ER小管中的高膜曲率和ER片的边缘来帮助维持ER结构。缺乏所有三种蛋白质的突变体显着改变了ER形态。我们发现,ER形状恢复在这个突变体时,Pex30 p或其同源Pex31 p过表达。Pex30 p在细胞内和重组成脂蛋白体时都能使细胞膜微管化,表明Pex30 p是一种新的ER成形蛋白。与网状蛋白相反,Pex30 p的丰度较低,我们发现它定位于ER的亚结构域。我们发现,这些ER子域的网站,大多数preperoxisomal囊泡(PPV)的产生。此外,Pex30p或Pex31p的过度产生或缺失会改变PPV的大小、形状和数量。我们的研究结果表明,Pex30p和Pex31p有助于形成和产生PPV生物发生的ER区域。
Joshi et al. show that Pex30p and Pex31p contain reticulon-like ER tubulating domains. Like reticulons, they localize to the edges of ER sheets and tubules but are only present in subdomains. These subdomains are devoid of reticulons and are the sites of pre-peroxisome vesicle biogenesis. Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like proteins that help maintain ER structure by stabilizing high membrane curvature in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has dramatically altered ER morphology. We found that ER shape is restored in this mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate membranes both in cells and when reconstituted into proteoliposomes, indicating that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p is low abundance, and we found that it localizes to subdomains in the ER. We show that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs) are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p help shape and generate regions of the ER where PPV biogenesis occurs.
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