A diffusion barrier maintains distribution of membrane proteins in polarized neurons
A diffusion barrier maintains distribution of membrane proteins in polarized neurons
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DOI：
10.1038/17789
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发表时间：
1999-02-25
期刊：
影响因子：
64.8
通讯作者：
Mellman, I
中科院分区：
文献类型：
--
作者：
Winckler, B;Forscher, P;Mellman, I
蛋白质在质膜不同区域的不对称分布对许多极化细胞的功能至关重要。在上皮细胞中，不同的顶侧和基底侧表面由紧密连接维持，防止蛋白质和脂质在两个结构域之间扩散（1）。极化神经元维持轴突和体树突质膜域没有明显的物理屏障。事实上，人工脂质DiI在假定的区域边界（轴突丘）没有遇到扩散障碍（2）。通过测量膜蛋白的横向流动性，使用光镊，我们在这里表明，一些膜蛋白表现出显着降低的流动性在轴突的初始段。破坏F-肌动蛋白和低水平的二甲基亚砜（DMSO）废除这种扩散屏障，并导致重新分配的膜标记，以前已极化。固定在初始段可能反映，至少部分，差异拴系细胞骨架成分。因此，维持膜蛋白极化分布的能力取决于轴突初始段的专门结构域，其限制侧向移动性并作为在细胞-细胞接触不存在的情况下起作用的新型扩散屏障。
The asymmetric distribution of proteins to distinct domains in the plasma membrane is crucial to the function of many polarized cells. In epithelia, distinct apical and basolateral surfaces are maintained by tight junctions that prevent diffusion of proteins and lipids between the two domains(1). Polarized neurons maintain axonal and somatodendritic plasma membrane domains without an obvious physical barrier. Indeed, the artificial lipid DiI encounters no diffusion barrier at the presumptive domain boundary, the axon hillock(2). By measuring the lateral mobility of membrane proteins using optical tweezers, we show here that some membrane proteins exhibit markedly reduced mobility in the initial segment of the axon. Disruption of F-actin and low levels of dimethyl sulphoxide (DMSO) abolish this diffusion barrier and lead to redistribution of membrane markers that had previously been polarized. Immobilization in the initial segment may reflect, at least in part, differential tethering to cytoskeletal components. Therefore, the ability to maintain a polarized distribution of membrane proteins depends on a specialized domain at the initial segment of the axon, which restricts lateral mobility and serves as a new type of diffusion barrier that acts in the absence of cell-cell contact.