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早期分泌途径和高尔基体膜与微管及微管马达蛋白的相互作用。

Interaction of early secretory pathway and Golgi membranes with microtubules and microtubule motors.

作者信息

Fokin A I, Brodsky I B, Burakov A V, Nadezhdina E S

机构信息

Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow, 119991, Russia.

出版信息

Biochemistry (Mosc). 2014 Sep;79(9):879-93. doi: 10.1134/S0006297914090053.

Abstract

This review summarizes the data describing the role of cellular microtubules in transportation of membrane vesicles - transport containers for secreted proteins or lipids. Most events of early vesicular transport in animal cells (from the endoplasmic reticulum to the Golgi apparatus and in the opposite recycling direction) are mediated by microtubules and microtubule motor proteins. Data on the role of dynein and kinesin in early vesicle transport remain controversial, probably because of the differentiated role of these proteins in the movements of vesicles or membrane tubules with various cargos and at different stages of secretion and retrograde transport. Microtubules and dynein motor protein are essential for maintaining a compact structure of the Golgi apparatus; moreover, there is a set of proteins that are essential for Golgi compactness. Dispersion of ribbon-like Golgi often occurs under physiological conditions in interphase cells. Golgi is localized in the leading part of crawling cultured fibroblasts, which also depends on microtubules and dynein. The Golgi apparatus creates its own system of microtubules by attracting γ-tubulin and some microtubule-associated proteins to membranes. Molecular mechanisms of binding microtubule-associated and motor proteins to membranes are very diverse, suggesting the possibility of regulation of Golgi interaction with microtubules during cell differentiation. To illustrate some statements, we present our own data showing that the cluster of vesicles induced by expression of constitutively active GTPase Sar1a[H79G] in cells is dispersed throughout the cell after microtubule disruption. Movement of vesicles in cells containing the intermediate compartment protein ERGIC53/LMANI was inhibited by inhibiting dynein. Inhibiting protein kinase LOSK/SLK prevented orientation of Golgi to the leading part of crawling cells, but the activity of dynein was not inhibited according to data on the movement of ERGIC53/LMANI-marked vesicles.

摘要

本综述总结了描述细胞微管在膜泡运输中作用的数据,膜泡是分泌蛋白或脂质的运输容器。动物细胞中早期囊泡运输的大多数事件(从内质网到高尔基体以及相反的循环方向)是由微管和微管运动蛋白介导的。动力蛋白和驱动蛋白在早期囊泡运输中的作用数据仍存在争议,可能是因为这些蛋白质在含有各种货物的囊泡或膜小管的运动以及分泌和逆行运输的不同阶段发挥着不同的作用。微管和动力蛋白运动蛋白对于维持高尔基体的紧密结构至关重要;此外,还有一组蛋白质对于高尔基体的紧密性必不可少。在间期细胞的生理条件下,带状高尔基体经常会发生分散。高尔基体位于爬行的培养成纤维细胞的前端,这也依赖于微管和动力蛋白。高尔基体通过将γ-微管蛋白和一些微管相关蛋白吸引到膜上来创建自己的微管系统。微管相关蛋白和运动蛋白与膜结合的分子机制非常多样,这表明在细胞分化过程中可能存在调节高尔基体与微管相互作用的可能性。为了说明一些观点,我们展示了自己的数据,即细胞中组成型活性GTP酶Sar1a[H79G]表达诱导的囊泡簇在微管破坏后会分散到整个细胞中。通过抑制动力蛋白,抑制了含有中间区室蛋白ERGIC53/LMANI的细胞中囊泡的运动。抑制蛋白激酶LOSK/SLK阻止了高尔基体向爬行细胞前端的定向,但根据ERGIC53/LMANI标记囊泡的运动数据,动力蛋白的活性并未受到抑制。

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