Physiology and Function of the Tight Junction

Physiology and Function of the Tight Junction
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DOI:
10.1101/cshperspect.a002584
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发表时间:
2009-08-01
影响因子:
7.2
通讯作者:
Van Itallie, Christina M.
Van Itallie, Christina M.
中科院分区:
生物学1区
文献类型:
--
作者:
Anderson, James M.;Van Itallie, Christina M.

文献摘要

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对紧密连接的理解已经从它们作为惰性溶质障碍的历史认识演变到对它们的生理和生化复杂性的认识。许多蛋白质特异性地定位于紧密连接,包括细胞质肌动蛋白结合蛋白和粘附性跨膜蛋白。后者包括Claudins,这是一种关键的屏障蛋白。目前的信息表明,细胞旁屏障最有用的模型是有两个生理组件:一个是半径为4埃的电荷选择性小孔系统,另一个是由屏障中较大的不连续部分创建的第二条路径,缺乏电荷或大小区分。第一条途径受claudin表达模式的影响,第二条途径可能受不同的蛋白质和信号控制。最近关于claudin功能和致病突变的信息使人们对它们在屏障形成中的作用有了更全面的了解,但由于缺乏高分辨率的结构信息,进展受到阻碍。
Understanding of tight junctions has evolved from their historical perception as inert solute barriers to recognition of their physiological and biochemical complexity. Many proteins are specifically localized to tight junctions, including cytoplasmic actin-binding proteins and adhesive transmembrane proteins. Among the latter are claudins, which are critical barrier proteins. Current information suggests that the paracellular barrier is most usefully modeled as having two physiologic components: a system of charge-selective small pores, 4 angstrom in radius, and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination. The first pathway is influenced by claudin expression patterns and the second is likely controlled by different proteins and signals. Recent information on claudin function and disease-causing mutations have led to a more complete understanding of their role in barrier formation, but progress is impeded by lack of high resolution structural information.