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Liquid–liquid phase separation at the plasma membrane–cytosol interface: common players in adhesion, motility, and synaptic function
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2021-09-04 , DOI: 10.1016/j.jmb.2021.167228
Martina Ramella 1 , Lucrezia Maria Ribolla 1 , Ivan de Curtis 1
Affiliation  

Networks of scaffold proteins and enzymes assemble at the interface between the cytosol and specific sites of the plasma membrane, where these networks guide distinct cellular functions. Some of these plasma membrane–associated platforms (PMAPs) include shared core components that are able to establish specific protein–protein interactions, to produce distinct supramolecular assemblies regulating dynamic processes as diverse as cell adhesion and motility, or the formation and function of neuronal synapses. How cells organize such dynamic networks is still an open question. In this review we introduce molecular networks assembling at the edge of migrating cells, and at pre– and postsynaptic sites, which share molecular players that can drive the assembly of biomolecular condensates. Very recent experimental evidence has highlighted the emerging role of some of these multidomain/scaffold proteins belonging to the GIT, liprin-α and ELKS/ERC families as drivers of liquid–liquid phase separation (LLPS). The data point to an important role of LLPS: (i) in the formation of PMAPs at the edge of migrating cells, where LLPS appears to be involved in promoting protrusion and the turnover of integrin–mediated adhesions, to allow forward cell translocation; (ii) in the assembly of the presynaptic active zone and of the postsynaptic density deputed to the release and reception of neurotransmitter signals, respectively. The recent results indicate that LLPS at cytosol–membrane interfaces is suitable not only for the regulation of active cellular processes, but also for the continuous spatial rearrangements of the molecular interactions involved in these dynamic processes.



中文翻译:

质膜-胞质溶胶界面的液-液相分离:粘附、运动和突触功能的常见参与者

支架蛋白和酶的网络在细胞质和质膜的特定位点之间的界面组装,这些网络引导不同的细胞功能。其中一些质膜相关平台 (PMAP) 包括共享的核心组件,这些组件能够建立特定的蛋白质-蛋白质相互作用,产生不同的超分子组装体,调节动态过程,如细胞粘附和运动,或神经元突触的形成和功能. 细胞如何组织这种动态网络仍然是一个悬而未决的问题。在这篇综述中,我们介绍了在迁移细胞边缘以及突触前和突触后位点组装的分子网络,它们共享可以驱动生物分子凝聚物组装的分子参与者。最近的实验证据强调了属于 GIT、liprin-α 和 ELKS/ERC 家族的一些多域/支架蛋白作为液-液相分离 (LLPS) 驱动因子的新兴作用。数据表明 LLPS 的重要作用:(i)在迁移细胞边缘形成 PMAP,其中 LLPS 似乎参与促进整合素介导的粘附的突出和转换,以允许向前细胞易位;(ii) 在突触前活动区和突触后密度的组装中,分别负责神经递质信号的释放和接收。最近的结果表明,细胞质-膜界面的 LLPS 不仅适用于调节活跃的细胞过程,

更新日期:2021-09-04
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