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一种将定量显微镜和计算机模拟相结合的新方法揭示了Arf1依赖性高尔基体大小调控机制。

A novel combinatorial approach of quantitative microscopy and in silico modeling deciphers Arf1-dependent Golgi size regulation.

作者信息

Iyer Prasanna, Sutradhar Sabyasachi, Paul Raja, Bhattacharyya Dibyendu

机构信息

Department of Cell and Tumor Biology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC), Tata Memorial Centre, Plot No. 1 & 2, Sector 22, Kharghar, 410210, Navi Mumbai, Maharashtra, India.

Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, MH 400085, Mumbai, India.

出版信息

Eur Phys J E Soft Matter. 2019 Dec 12;42(12):154. doi: 10.1140/epje/i2019-11920-x.

DOI:10.1140/epje/i2019-11920-x
PMID:31834534
Abstract

Regulation of organelle size and shape is a poorly understood but fascinating subject. Several theoretical studies were reported on Golgi size regulation, but a combination of experimental and theoretical approaches is rare. In combination with the quantitative microscopy and a coarse-grained simulation model, we have developed a technique to gain insights into the functions of potential regulators of Golgi size in budding yeast Saccharomyces cerevisiae. To validate our method, we tested wild-type and arf1[Formula: see text] strain harboring early and late Golgi cisternae labeled with green and red fluorescent fusions. Our concentration-dependent maturation model prediction concurs with most of the experimental results for both wild-type and arf1[Formula: see text] strains. Decisive match of simulation and experimental data provide insight into such specific factor's function in regulating the Golgi size. Details of the complex multifactorial network of Golgi size regulation can be deciphered in the future using a similar combination of quantitative microscopy and in silico model.

摘要

细胞器大小和形状的调控是一个鲜为人知但引人入胜的课题。已有多项关于高尔基体大小调控的理论研究报道,但将实验方法与理论方法相结合的情况却很少见。结合定量显微镜技术和粗粒度模拟模型,我们开发了一种技术,以深入了解出芽酵母酿酒酵母中高尔基体大小潜在调控因子的功能。为了验证我们的方法,我们测试了携带用绿色和红色荧光融合蛋白标记的早期和晚期高尔基体潴泡的野生型和arf1[公式:见正文]菌株。我们的浓度依赖性成熟模型预测与野生型和arf1[公式:见正文]菌株的大多数实验结果一致。模拟和实验数据的决定性匹配为这种特定因子在调节高尔基体大小中的功能提供了见解。未来,使用定量显微镜技术和计算机模拟模型的类似组合,可以解读高尔基体大小调控复杂多因素网络的细节。

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A novel combinatorial approach of quantitative microscopy and in silico modeling deciphers Arf1-dependent Golgi size regulation.一种将定量显微镜和计算机模拟相结合的新方法揭示了Arf1依赖性高尔基体大小调控机制。
Eur Phys J E Soft Matter. 2019 Dec 12;42(12):154. doi: 10.1140/epje/i2019-11920-x.
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本文引用的文献

1
Stochastic Model of Maturation and Vesicular Exchange in Cellular Organelles.细胞细胞器中成熟和囊泡交换的随机模型。
Biophys J. 2018 Feb 27;114(4):947-957. doi: 10.1016/j.bpj.2017.12.018.
2
Golgi enlargement in Arf-depleted yeast cells is due to altered dynamics of cisternal maturation.内质网应激时肌醇需求的增加是通过激活 mTORC1 信号来实现的。
J Cell Sci. 2014 Jan 1;127(Pt 1):250-7. doi: 10.1242/jcs.140996. Epub 2013 Nov 4.
3
Quantitative analysis of intra-Golgi transport shows intercisternal exchange for all cargo.高尔基体内部运输的定量分析表明所有货物都存在小泡间交换。
Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15692-7. doi: 10.1073/pnas.1303358110. Epub 2013 Sep 9.
4
ARF1 and ARF4 regulate recycling endosomal morphology and retrograde transport from endosomes to the Golgi apparatus.ARF1 和 ARF4 调节再循环内体的形态和从内体到高尔基体的逆行运输。
Mol Biol Cell. 2013 Aug;24(16):2570-81. doi: 10.1091/mbc.E13-04-0197. Epub 2013 Jun 19.
5
ARF1 and ARF3 are required for the integrity of recycling endosomes and the recycling pathway.ARF1和ARF3是回收型内体的完整性及回收途径所必需的。
Cell Struct Funct. 2012;37(2):141-54. doi: 10.1247/csf.12015. Epub 2012 Sep 5.
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The yeast Golgi apparatus.酵母高尔基体。
Traffic. 2012 Apr;13(4):505-10. doi: 10.1111/j.1600-0854.2011.01316.x. Epub 2011 Dec 27.
7
A modeling approach to the self-assembly of the Golgi apparatus.一种高尔基体自组装的建模方法。
Biophys J. 2010 Jun 16;98(12):2839-47. doi: 10.1016/j.bpj.2010.03.035.
8
Arf1-GTP-induced tubule formation suggests a function of Arf family proteins in curvature acquisition at sites of vesicle budding.Arf1-GTP诱导的微管形成表明Arf家族蛋白在囊泡出芽位点的曲率获取中发挥作用。
J Biol Chem. 2008 Oct 10;283(41):27717-27723. doi: 10.1074/jbc.M804528200. Epub 2008 Aug 7.
9
Membrane curvature induced by Arf1-GTP is essential for vesicle formation.由Arf1 - GTP诱导的膜曲率对于囊泡形成至关重要。
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11731-6. doi: 10.1073/pnas.0805182105. Epub 2008 Aug 8.
10
Arfs and membrane lipids: sensing, generating and responding to membrane curvature.急性肾损伤与膜脂:感知、产生膜曲率并对其作出反应。
Biochem J. 2008 Sep 1;414(2):e1-2. doi: 10.1042/BJ20081438.