MECHANISMS FOR FORMATION OF CELL MEMBRANE DOMAINS

说明(改编自摘要)： 细胞表面调节信息和代谢物的流动。 细胞与其环境之间的关系。细胞表面膜模型 是从强调膜的流动性和自主性演变而来的 组成分子，到另一个强调侧向的分子 将膜蛋白和脂类浓缩到贴片中， 通常被解释为表明这些分子被限制在 膜结构域。虽然各种实验都报告了 膜结构域，斑块形成的机制，以及通过 暗示，域创建的机制在很大程度上是未知的。 分子之间的特定相互作用参与了这种形成 非常小的蛋白质或脂肪斑块，但其机制 创造大的膜结构域，直径为100纳米，是未知的。 如果不了解这些机制，就无法理解 膜结构域对细胞表面膜的重要性或相关性 在正常和异常细胞中发挥作用。 PI开发了一个模型，一个基于 细胞质中大规模结构域形成的实验数据 膜。该模型假定膜之间没有特定的相互作用。 蛋白质和脂类。相反，它取决于横向扩散。 膜蛋白和膜脂的系数，在发生和 横向移动障碍物的稳定性，以及对水泡流量的稳定性 从表面上看。PI发现囊泡流量和 需要建立和维护横向移动的动态障碍 膜的横向不均匀性与100s的纳米磁区一致 在直径上。在没有横向移动障碍或 囊泡交通，横向扩散随机化分布 膜分子。该模型暗示，表观浓度 膜结构域中的蛋白质和脂类可能是非特异性的 膜物理和细胞新陈代谢的结果。 PI建议使用细胞来测试他的模型，在这些细胞中，屏障可以 侧方活动能力有缺陷，Sph/Sph，α-血影蛋白缺乏， 红白血病细胞，以及囊泡进出的细胞 表面被抑制。

DESCRIPTION (Adapted from abstract): The cell surface mediates the flow of information and metabolites between a cell and its environment. The model of cell surface membranes is evolving from one that emphasizes mobility and autonomy of membrane constituent molecules, to another that emphasizes the lateral concentration of membrane proteins and lipids into patches that are often interpreted as showing that these molecules are confined in membrane domains. While a variety of experiments report the existence of membrane domains, the mechanisms of patch formation, and by implication, the mechanisms of domain creation are largely unknown. Specific interactions between molecules are involved in the formation of very small patches of proteins or lipid but the mechanisms that create large membrane domains, 100s of nm in diameter, are unknown. Without understanding these mechanisms one cannot understand the importance or relevance of membrane domains for cell surface membrane function in normal and abnormal cells. The PI has developed a model, a numerical simulation model based on experimental data, for large-scale domain formation in cell plasma membranes. The model assumes no specific interactions between membrane proteins and lipids. Rather, it depends upon the lateral diffusion coefficients of membrane proteins and lipids, upon the occurrence and stability of barriers to lateral mobility, and upon vesicle traffic to and from the surface. The PI finds that both vesicle traffic, and dynamic barriers to lateral mobility are required to create and maintain lateral heterogeneities in membranes consistent with domains 100s of nm in diameter. In the absence of either barriers to lateral mobility or vesicle traffic, lateral diffusion randomizes the distribution of membrane molecules. The model implies that the apparent concentration of proteins and lipids in membrane domains may be a nonspecific consequence of membrane physics and cell metabolism. The PI proposes to test his model using cells in which the barriers to lateral mobility are defective, sph/sph, alpha-spectrin-deficient, erythroleukemia cells, and cells in which vesicle traffic from and to the surface is inhibited.