Molecular model of the microvillar cytoskeleton and organization of the brush border.

Molecular model of the microvillar cytoskeleton and organization of the brush border.
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DOI:
10.1371/journal.pone.0009406
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发表时间:
2010-02-24
期刊:
影响因子:
3.7
通讯作者:
McKnight CJ
McKnight CJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brown JW;McKnight CJ

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刷状边缘微绒毛是从某些特殊的吸收上皮细胞的顶端表面发出的∼1-微米长的指状突起。由数千个这种大小均匀的结构组成的高度对称的六角形阵列形成了灌木丛边缘,除了有助于营养吸收外,还保护大面积的表面积免受病原体的侵袭。在这里,我们提出了一个蛋白质细胞骨架的分子模型,负责这种戏剧性的细胞形态。该模型是根据过去30多年来几个研究小组报告的已发表的结晶学和微观结构构建的。我们的努力导致了肌动蛋白、纤毛蛋白、绒毛蛋白、刷状边缘肌球蛋白(Myo1A)、钙调蛋白和刷状边缘幽灵蛋白的单一、独特、自洽的排列。支持微绒毛的中央肌动蛋白核心束几乎饱和了纤毛蛋白和绒毛蛋白交联剂,其密度与蛋白质晶体中的密度相似。所提出的模型考虑了所有主要的蛋白质组分,再现了实验确定的化学计量比,并与生物刷子边界膜的大小和形态一致。本文提出的模型将作为一个结构框架来解释在几个时间尺度上发生的许多动态细胞过程,例如蛋白质的扩散、结合和周转、脂筏分选、膜变形、细胞骨架-膜相互作用,甚至是入侵病原体对刷状边界的消失。此外,该模型为评估导致高度动态微绒毛的统一大小和结构的平衡过程提供了结构基础。
Brush border microvilli are ∼1-µm long finger-like projections emanating from the apical surfaces of certain, specialized absorptive epithelial cells. A highly symmetric hexagonal array of thousands of these uniformly sized structures form the brush border, which in addition to aiding in nutrient absorption also defends the large surface area against pathogens. Here, we present a molecular model of the protein cytoskeleton responsible for this dramatic cellular morphology. The model is constructed from published crystallographic and microscopic structures reported by several groups over the last 30+ years. Our efforts resulted in a single, unique, self-consistent arrangement of actin, fimbrin, villin, brush border myosin (Myo1A), calmodulin, and brush border spectrin. The central actin core bundle that supports the microvillus is nearly saturated with fimbrin and villin cross-linkers and has a density similar to that found in protein crystals. The proposed model accounts for all major proteinaceous components, reproduces the experimentally determined stoichiometry, and is consistent with the size and morphology of the biological brush border membrane. The model presented here will serve as a structural framework to explain many of the dynamic cellular processes occurring over several time scales, such as protein diffusion, association, and turnover, lipid raft sorting, membrane deformation, cytoskeletal-membrane interactions, and even effacement of the brush border by invading pathogens. In addition, this model provides a structural basis for evaluating the equilibrium processes that result in the uniform size and structure of the highly dynamic microvilli.
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发表时间: 1980-01-01
期刊: CELL
影响因子: 64.5
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