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The influence of phosphatidylserine localisation and lipid phase on membrane remodelling by the ESCRT-II/ESCRT-III complex
Faraday Discussions ( IF 3.3 ) Pub Date : 2020-07-14 , DOI: 10.1039/d0fd00042f
Andrew Booth 1 , Christopher J Marklew 2 , Barbara Ciani 2 , Paul A Beales 1, 3
Affiliation  

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.

中文翻译:

磷脂酰丝氨酸定位和脂质相对 ESCRT-II/ESCRT-III 复合物膜重塑的影响

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,以驱动膜内陷和腔内囊泡 (ILV) 的断裂,这一过程也受膜力学控制。然而,ESCRT 与膜的结合也是由与阴离子磷脂的静电相互作用介导的。由于例如脂筏的形成和曲率驱动的脂质分选,天然生物膜内的磷脂分布是不均匀的。在这里,我们使用相分离的巨型单层囊泡 (GUV) 来研究富含磷脂酰丝氨酸 (PS) 的脂质结构域与 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,d ) 和/或液体有序 (L o ) 域,分别。共存相之间的 PS 分配由荧光膜联蛋白 V 探针确认。最终,我们发现当 PS 脂质定位于 L d域内时,ESCRT 促进的 ILV 生成显着增强。然而,形成的 ILV 富含 L o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 L o相的优先募集,因为它增加了刚性,其中 L d相在所得芽的颈部有利于促进膜的这些区域中的高膜曲率。 ILV 形成过程。Ld _结构域对膜弯曲的抵抗力较低,证明了一种机制,通过该机制,膜的组成和力学可以耦合以调节 ESCRT 活动的位置和效率。
更新日期:2020-07-14
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