Small G proteins in peroxisome biogenesis: the potential involvement of ADP-ribosylation factor 6.

Small G proteins in peroxisome biogenesis: the potential involvement of ADP-ribosylation factor 6.
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DOI:
10.1186/1471-2121-10-58
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发表时间:
2009-08-17
期刊:
影响因子:
--
通讯作者:
Fransen M
Fransen M
中科院分区:
生物3区
文献类型:
--
作者:
Anthonio EA;Brees C;Baumgart-Vogt E;Hongu T;Huybrechts SJ;Van Dijck P;Mannaerts GP;Kanaho Y;Van Veldhoven PP;Fransen M

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过氧化物酶体在几乎每一种真核生物中都发挥着不同的重要功能。新的过氧化物酶体通过从预先存在的细胞器出芽或通过ER的囊泡化从头形成。已表明ADP-核糖基化因子和COPI外被体复合物参与这些过程。在这里,我们表明,所有可行的酿酒酵母菌株缺陷的一个小GTP酶有一个重要的作用,在调节囊泡运输含有功能过氧化物酶体,这些细胞器在油酸生长的细胞的数量显着上调arf 1和arf 3空菌株相比,野生型菌株。此外,我们提供的证据表明,一部分内源性Arf 6,酵母Arf 3的哺乳动物直向同源物,与大鼠肝脏过氧化物酶体的细胞质面。尽管如此,消融Arf 6既不影响过氧化物酶体丰度的调节,也不影响过氧化物酶体蛋白在培养的胎肝细胞中的定位。然而,野生型,GTP水解缺陷型或(显性阴性)GTP结合缺陷型Arf 1和Arf 6的共过表达引起新合成的过氧化物酶体蛋白的错误定位,并导致过氧化物酶体形态的改变。这些观察结果表明,Arf 6是哺乳动物过氧化物酶体生物合成的关键球员。此外,他们还提供了强有力的支持和扩展的概念,具体的Arf亚型对可能会采取行动,在串联调节独家贩运途径。
Peroxisomes execute diverse and vital functions in virtually every eukaryote. New peroxisomes form by budding from pre-existing organelles or de novo by vesiculation of the ER. It has been suggested that ADP-ribosylation factors and COPI coatomer complexes are involved in these processes. Here we show that all viable Saccharomyces cerevisiae strains deficient in one of the small GTPases which have an important role in the regulation of vesicular transport contain functional peroxisomes, and that the number of these organelles in oleate-grown cells is significantly upregulated in the arf1 and arf3 null strains compared to the wild-type strain. In addition, we provide evidence that a portion of endogenous Arf6, the mammalian orthologue of yeast Arf3, is associated with the cytoplasmic face of rat liver peroxisomes. Despite this, ablation of Arf6 did neither influence the regulation of peroxisome abundance nor affect the localization of peroxisomal proteins in cultured fetal hepatocytes. However, co-overexpression of wild-type, GTP hydrolysis-defective or (dominant-negative) GTP binding-defective forms of Arf1 and Arf6 caused mislocalization of newly-synthesized peroxisomal proteins and resulted in an alteration of peroxisome morphology. These observations suggest that Arf6 is a key player in mammalian peroxisome biogenesis. In addition, they also lend strong support to and extend the concept that specific Arf isoform pairs may act in tandem to regulate exclusive trafficking pathways.
拟南芥肌球蛋白XI的同工型与其C末端尾部区域的小GTPase相互作用。
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