Modulation of a host’s cell membrane nano-environment by mycobacterial glycolipids: involvement of PI(4,5)P2 signaling lipid?,Faraday Discussions

当前位置： X-MOL 学术 › Faraday Discuss. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Modulation of a host’s cell membrane nano-environment by mycobacterial glycolipids: involvement of PI(4,5)P2 signaling lipid?
Faraday Discussions ( IF 3.3 ) Pub Date : 2020-06-30 , DOI: 10.1039/d0fd00051e
Manjari Mishra ₁ , Shobhna Kapoor ₁

Affiliation

Virulence-associated glycolipids from Mycobacterium tuberculosis (Mtb) act as effector molecules during infection—in addition to proteins. Upon insertion, they alter the host cell’s membrane properties modifying the host’s functions to aid Mtb survival and disease course. Here we combine tether force experiments and microscopy to reveal previously unknown insights on the potential involvement of the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) lipid in the Mtb lipid–host interaction landscape. Our data shows that Mtb lipids, having different structural and chemical make-up, distinctly alter a host’s PI(4,5)P₂ membrane abundance/organization and PI(4,5)P₂-actin colocalization, thus impacting the plasma membrane–cytoskeletal adhesion forces. Combined with our previous findings that underscore the role of exogenous Mtb lipids in remodeling host plasma membrane organization and mechanics, this work builds upon a lipid-centric view of tubercular infections. Dynamically changing a host’s plasma membrane lipid content – in response to virulent lipids – might represent a so far unexplored mechanism invoked by Mtb to modulate the host cell’s adhesive properties to escape immune surveillance. These findings will deepen our collective understanding of the functional role of Mtb lipids in hijacking the host cell processes amenable to pharmacological inhibition.

中文翻译：

分枝杆菌糖脂对宿主细胞膜纳米环境的调节：PI(4,5)P2信号脂质的参与？

除蛋白质外，来自结核分枝杆菌( Mtb )的毒力相关糖脂在感染期间充当效应分子。插入后，它们会改变宿主细胞的膜特性，从而改变宿主的功能，以帮助Mtb存活和疾病进程。在这里，我们结合系绳力实验和显微镜来揭示以前未知的关于磷脂酰肌醇 4,5-二磷酸 (PI(4,5)P ₂ ) 脂质在Mtb脂质-宿主相互作用景观中的潜在参与的见解。我们的数据表明，具有不同结构和化学组成的Mtb脂质明显改变宿主的 PI(4,5)P ₂膜丰度/组织和 PI(4,5)P ₂ -肌动蛋白共定位，从而影响质膜-细胞骨架粘附力。结合我们之前强调外源性Mtb脂质在重塑宿主质膜组织和力学中的作用的发现，这项工作建立在以脂质为中心的结核感染观点之上。动态改变宿主的质膜脂质含量 - 以响应毒性脂质 - 可能代表了Mtb调用的一种迄今为止尚未探索的机制，以调节宿主细胞的粘附特性以逃避免疫监视。这些发现将加深我们对Mtb功能作用的集体理解劫持宿主细胞过程中的脂质可以进行药理学抑制。

更新日期：2020-06-30

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11