Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa Lisboa, Portugal.
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique Toulouse, France ; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse III (Paul Sabatier) Toulouse, France.
Front Plant Sci. 2014 Mar 5;5:72. doi: 10.3389/fpls.2014.00072. eCollection 2014.
To date, it is widely accepted that microdomains do form in the biological membranes of all eukaryotic cells, and quite possibly also in prokaryotes. Those sub-micrometric domains play crucial roles in signaling, in intracellular transport, and even in inter-cellular communications. Despite their ubiquitous distribution, and the broad and lasting interest invested in those microdomains, their actual nature and composition, and even the physical rules that regiment their assembly still remain elusive and hotly debated. One of the most often considered models is the raft hypothesis, i.e., the partition of lipids between liquid disordered and ordered phases (Ld and Lo, respectively), the latter being enriched in sphingolipids and cholesterol. Although it is experimentally possible to obtain the formation of microdomains in synthetic membranes through Ld/Lo phase separation, there is an ever increasing amount of evidence, obtained with a wide array of experimental approaches, that a partition between domains in Ld and Lo phases cannot account for many of the observations collected in real cells. In particular, it is now commonly perceived that the plasma membrane of cells is mostly in Lo phase and recent data support the existence of gel or solid ordered domains in a whole variety of live cells under physiological conditions. Here, we present a model whereby seeds comprised of oligomerised proteins and/or lipids would serve as crystal nucleation centers for the formation of diverse gel/crystalline nanodomains. This could confer the selectivity necessary for the formation of multiple types of membrane domains, as well as the stability required to match the time frames of cellular events, such as intra- or inter-cellular transport or assembly of signaling platforms. Testing of this model will, however, require the development of new methods allowing the clear-cut discrimination between Lo and solid nanoscopic phases in live cells.
迄今为止，人们普遍认为，真核细胞的生物膜中确实会形成微区，原核生物中也很可能会形成微区。这些亚微米区域在信号转导、细胞内运输甚至细胞间通讯中都起着至关重要的作用。尽管这些微区分布广泛，人们对它们的兴趣也非常广泛且持久，但它们的实际性质和组成，甚至调控它们组装的物理规则仍然难以捉摸，且存在激烈的争论。最常被考虑的模型之一是筏模型，即脂质在无序相和有序相（分别为 Ld 和 Lo）之间的分配，后者富含鞘脂和胆固醇。虽然通过 Ld/Lo 相分离在人工膜中获得微区形成是可行的实验操作，但越来越多的证据表明，Ld 和 Lo 相之间的域分离不能解释许多在真实细胞中收集到的观察结果。特别是，现在普遍认为细胞的质膜主要处于 Lo 相，最近的数据支持在生理条件下各种活细胞中存在凝胶或固态有序域。在这里，我们提出了一个模型，其中由寡聚化蛋白和/或脂质组成的“种子”可以作为形成各种凝胶/结晶纳米域的晶体成核中心。这可以赋予形成多种类型的膜域所需的选择性，以及与细胞事件（如细胞内或细胞间运输或信号平台组装）的时间框架相匹配所需的稳定性。然而，对该模型的测试将需要开发新的方法，以便在活细胞中清楚地区分 Lo 和固态纳米相。
