The influence of phosphatidylserine localisation and lipid phase on membrane remodelling by the ESCRT-II/ESCRT-III complex
The influence of phosphatidylserine localisation and lipid phase on membrane remodelling by the ESCRT-II/ESCRT-III complex
复制标题
磷脂酰丝氨酸定位和脂相对 ESCRT-II/ESCRT-III 复合物膜重塑的影响
DOI：
10.1101/2020.04.21.053389
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Booth A
中科院分区：
文献类型：
--
作者：
Booth A
转运所需的内体分选复合物（ESCRT）在脂质双层表面上以超分子结构组织，以驱动膜内陷和管腔内囊泡（ILV）的断裂，该过程也由膜力学控制。然而，ESCRT协会与膜也介导的静电相互作用与阴离子磷脂。天然生物膜内的磷脂分布是不均匀的，这是由于例如脂筏的形成和曲率驱动的脂质分选。在这里，我们已经使用相分离的巨型单层囊泡（GUV），研究磷脂酰丝氨酸（PS）丰富的脂质结构域和ESCRT活性之间的联系。我们采用由相分离脂质混合物组成的GUV，其中不饱和DOPS和饱和DPPS脂质单独或同时掺入以分别增强PS在液体无序（Ld）和/或液体有序（Lo）结构域中的定位。通过荧光膜联蛋白V探针确认共存相之间的PS分配。最终，我们发现，ILV代促进ESCRTs是显着增强PS脂质定位在LD域。然而，形成的ILV富含Lo脂质。我们将这一令人惊讶的观察结果解释为ESCRT复合物下方的Lo相由于其增加的刚性而优先募集，其中Ld相在所得芽的颈部中是有利的，以在ILV形成过程期间促进膜的这些区域中的高膜曲率。LD结构域提供较低的膜弯曲阻力，证明了一种机制，通过该机制，膜的组成和力学可以耦合到调节ESCRT活性的位置和效率。
The endosomal sorting complex required for transport (ESCRT) organises in supramolecular structures on the surface of lipid bilayers to drive membrane invagination and scission of intraluminal vesicles (ILVs), a process also controlled by membrane mechanics. However, ESCRT association with the membrane is also mediated by electrostatic interactions with anionic phospholipids. Phospholipid distribution within natural biomembranes is inhomogeneous due to, for example, the formation of lipid rafts and curvature-driven lipid sorting. Here, we have used phase-separated giant unilamellar vesicles (GUVs) to investigate the link between phosphatidylserine (PS)-rich lipid domains and ESCRT activity. We employ GUVs composed of phase separating lipid mixtures, where unsaturated DOPS and saturated DPPS lipids are incorporated individually or simultaneously to enhance PS localisation in liquid disordered (Ld) and/or liquid ordered (Lo) domains, respectively. PS partitioning between the coexisting phases is confirmed by a fluorescent Annexin V probe. Ultimately, we find that ILV generation promoted by ESCRTs is significantly enhanced when PS lipids localise within Ld domains. However, the ILVs that form are rich in Lo lipids. We interpret this surprising observation as preferential recruitment of the Lo phase beneath the ESCRT complex due to its increased rigidity, where the Ld phase is favoured in the neck of the resultant buds to facilitate the high membrane curvature in these regions of the membrane during the ILV formation process. Ld domains offer lower resistance to membrane bending, demonstrating a mechanism by which the composition and mechanics of membranes can be coupled to regulate the location and efficiency of ESCRT activity.
登录
查看更多内容
影响因子：
3.4
作者：
R. D. Usery;T. A. Enoki;S. Wickramasinghe;V. Nguyen;David G. Ackerman;D. Greathouse;R. Koeppe;F. Barrera;G. Feigenson
通讯作者：
R. D. Usery;T. A. Enoki;S. Wickramasinghe;V. Nguyen;David G. Ackerman;D. Greathouse;R. Koeppe;F. Barrera;G. Feigenson
神奇的核膜突出以及在哪里可以找到它们。
影响因子：
3.9
作者：
Thaller,DavidJ;PatrickLusk,C
通讯作者：
PatrickLusk,C
影响因子：
11.8
作者：
Buchkovich, Nicholas J.;Henne, William Mike;Emr, Scott D.
通讯作者：
Emr, Scott D.
影响因子：
8.6
作者：
Veatch, SL;Keller, SL
通讯作者：
Keller, SL
影响因子：
3.4
作者：
Baumgart, Tobias;Hunt, Geoff;Feigenson, Gerald W.
通讯作者：
Feigenson, Gerald W.