PDF(Pubmed)
Abstract：
Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.
摘要：
脂膜纳米域或脂筏是10-200nm直径大小的胆固醇-和鞘脂-富集的域的质膜，收集许多具有不同作用的蛋白质。通过差速离心和蛋白质组学研究分离和表征质膜蛋白质，揭示了这些结构域中蛋白质的显着多样性。脂质膜纳米结构域的有限尺寸挑战了所有它们可以共存于同一脂质膜结构域内的简单可能性。作为caveolin-1，flotillin亚型和神经节苷脂目前被用作神经元脂质膜纳米结构域标记，我们首先分析了在质膜形成纳米域的这些组分的结构特征，因为它们与构建由这些分子特征构成的超分子复合物有关。在与神经元脂质膜纳米结构域相关的蛋白质中，有大量的蛋白质在钙信号中起主要作用，如神经递质的离子和代谢受体，钙通道,和钙泵。这篇综述强调了与分离的caveolin-1和floillin-lipid膜纳米结构域相关的钙信号蛋白之间的巨大差异。由于这些钙信号蛋白分散在神经元质膜的不同位置，即，在突触前，突触后，轴突或树突树，或者在神经元体细胞中，我们的分析表明,不同的脂质膜结构域亚型应该存在于神经元中.此外，我们得出的结论是，通过在钙信号蛋白中的含量对脂质膜结构域进行分类，揭示了这些结构域在神经元活动中的作用，这些作用取决于细胞内钙浓度。这篇综述中描述的一些例子包括突触和代谢活动，神经递质和神经调质的分泌，神经元兴奋性（长期增强和长期抑郁），轴突和树突生长，但也神经元细胞存活和死亡。
