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Visualizing sphingolipid biosynthesis in cells
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2018-11-23 , DOI: 10.1016/j.chemphyslip.2018.11.003
Seetharaman Parashuraman , Giovanni D’Angelo

Biosynthetic pathways play a fundamental role in the building and operation of the cell by synthesizing the constituents by which the cell is constructed, and by producing signalling intermediates that play a key role in cell regulation. While a lot is known about the metabolite profile of the cells and about the biochemical pathways through which these metabolites are produced, the cellular localization of the biosynthetic machineries and the importance of this localization to the regulation of the metabolism has often been given less attention. This derives from the fact that, for several of these pathways, the enzymes involved are found colocalized in one compartment where their specific localization is unlikely to influence their function. The sphingolipid (SL) metabolic pathway is a notable exception to this as SL synthetic enzymes are laid out on a specific pattern across the secretory compartments. Such compartmentalized organization of the SL synthesis has functional implications as it makes the fine-tuned regulation of the process possible by allowing cells to regulate specific segments of the pathway in response to stimuli and for adaptation. The organization, dynamics, and regulation of the SLs and their biosynthetic machinery have been investigated using imaging-based methods. Here we provide a brief introduction to the techniques that have been or that could be employed to visualize the SL biosynthetic machinery and SLs themselves and discuss the insights provided by these studies in understanding this metabolism.



中文翻译:

可视化细胞中鞘脂的生物合成

生物合成途径通过合成构建细胞的成分,并通过产生在细胞调节中起关键作用的信号传导中间体,在细胞的构建和运行中起着基本作用。尽管人们对细胞的代谢产物概况以及产生这些代谢产物的生化途径了解很多,但生物合成机械的细胞定位及其对代谢调节的重要性通常很少受到关注。这源于以下事实:对于这些途径中的几种,发现所涉及的酶共定位在一个区室中,在该区室中其特定的定位不太可能影响其功能。鞘脂(SL)代谢途径是一个明显的例外,因为SL合成酶以特定的模式分布在整个分泌室中。SL合成的这种分隔组织具有功能含义,因为它通过允许细胞响应刺激和适应而调节途径的特定片段,从而使过程的精细调节成为可能。SL的组织,动力学和调控及其生物合成机制已使用基于成像的方法进行了研究。在这里,我们简要介绍了已经或可以用来可视化SL生物合成机制和SL本身的技术,并讨论了这些研究在理解这种新陈代谢中提供的见解。SL合成的这种分隔组织具有功能含义,因为它通过允许细胞响应刺激和适应而调节途径的特定片段,从而使过程的精细调节成为可能。SL的组织,动力学和调控及其生物合成机制已使用基于成像的方法进行了研究。在这里,我们简要介绍了已经或可以用来可视化SL生物合成机制和SL本身的技术,并讨论了这些研究在理解这种新陈代谢中提供的见解。SL合成的这种分隔组织具有功能含义,因为它通过允许细胞响应刺激和适应而调节途径的特定片段,从而使过程的精细调节成为可能。SL的组织,动力学和调控及其生物合成机制已使用基于成像的方法进行了研究。在这里,我们简要介绍了已经或可以用来可视化SL生物合成机制和SL本身的技术,并讨论了这些研究在理解这种新陈代谢中提供的见解。

更新日期:2018-11-23
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