Just Wilhelm W, Peränen Johan
Biochemistry Center Heidelberg (BZH), University of Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Institute of Biotechnology, University of Helsinki, Viikinkaari 9, FIN00014 Helsinki, Finland.
Biochim Biophys Acta. 2016 May;1863(5):1006-13. doi: 10.1016/j.bbamcr.2016.01.004. Epub 2016 Jan 8.
In this review article, we summarize current knowledge on peroxisome biogenesis/functions and the role that small GTPases may play in these processes. Precise intracellular distribution of cell organelles requires their regulated association to microtubules and the actin cytoskeleton. In this respect, RhoGDP/RhoGTP favor binding of peroxisomes to microtubules and actin filaments. In its GTP-bound form, RhoA activates a regulatory cascade involving Rho kinaseII and non-muscle myosinIIA. Such interactions frequently depend on phosphoinositides (PIs) of which PI4P, PI(4,5)P2, and PI(3,5)P2 were found to be present in the peroxisomal membrane. PIs are pivotal determinants of intracellular signaling and known to regulate a wide range of cellular functions. In many of these functions, small GTPases are implicated. The small GTPase ADP-ribosylation factor 1 (Arf1), for example, is known to stimulate synthesis of PI4P and PI(4,5)P2 on the Golgi to regulate protein and lipid sorting. In vitro binding assays localized Arf1 and the COPI complex to peroxisomes. In light of the recent discussion of pre-peroxisomal vesicle generation at the ER, peroxisomal Arf1-COPI vesicles may serve retrograde transport of ER-resident components. A mass spectrometric screen localized various Rab proteins to peroxisomes. Overexpression of these proteins in combination with laser-scanning fluorescence microscopy co-localized Rab6, Rab8, Rab10, Rab14, and Rab18 with peroxisomal structures. By analogy to the role these proteins play in other organelle dynamics, we may envisage what the function of these proteins may be in relation to the peroxisomal compartment.
在这篇综述文章中，我们总结了目前关于过氧化物酶体生物发生/功能的知识，以及小GTP酶在这些过程中可能发挥的作用。细胞器在细胞内的精确分布需要它们与微管和肌动蛋白细胞骨架进行调控关联。在这方面，RhoGDP/RhoGTP有利于过氧化物酶体与微管和肌动蛋白丝的结合。RhoA以其GTP结合形式激活一个涉及Rho激酶II和非肌肉肌球蛋白IIA的调控级联反应。这种相互作用通常依赖于磷酸肌醇（PIs），其中PI4P、PI(4,5)P2和PI(3,5)P2被发现存在于过氧化物酶体膜中。PIs是细胞内信号传导的关键决定因素，已知可调节广泛的细胞功能。在许多这些功能中，小GTP酶都有涉及。例如，小GTP酶ADP核糖基化因子1（Arf1）已知可刺激高尔基体上PI4P和PI(4,5)P2的合成，以调节蛋白质和脂质分选。体外结合试验将Arf1和COPI复合体定位到过氧化物酶体。鉴于最近关于内质网处过氧化物酶体前体囊泡生成的讨论，过氧化物酶体Arf1-COPI囊泡可能用于内质网驻留成分的逆行运输。质谱筛选将多种Rab蛋白定位到过氧化物酶体。这些蛋白的过表达与激光扫描荧光显微镜相结合，使Rab6、Rab8、Rab10、Rab14和Rab18与过氧化物酶体结构共定位。通过类比这些蛋白在其他细胞器动态变化中所起的作用，我们可以设想这些蛋白与过氧化物酶体区室相关的功能可能是什么。
