Molecular physiology and pathophysiology of tight junctions - I. Biogenesis of tight junctions and epithelial polarity
Molecular physiology and pathophysiology of tight junctions - I. Biogenesis of tight junctions and epithelial polarity
复制标题
DOI：
10.1152/ajpgi.2000.279.3.g477
复制
发表时间：
2000-09-01
影响因子：
4.5
通讯作者：
Contreras, RG
中科院分区：
文献类型：
--
作者：
Cereijido, M;Shoshani, L;Contreras, RG
紧密连接（TJ）首先通过其控制跨细胞旁途径渗透的能力而被注意到，但其分子组分与参与肿瘤抑制、核寻址和细胞增殖的肽的同源性表明它可能参与许多其他基本功能。TJ由十几种分子种类形成，这些分子种类通过PDZ和其他蛋白质-蛋白质聚类促进序列组装，以响应E-钙粘蛋白的激活。TJ占据顶端和基底外侧域之间的高度特异性的位置。它的第一个分子组分似乎是通过寻址其分子中的信号传递到这样的位置，并且一旦锚定，就作为进一步TJ相关分子的聚集核。虽然在成熟的上皮细胞中TJ和E-钙粘蛋白不共定位，但复杂的反应链从一个到另一个，涉及α-、β-和γ-连环蛋白，两种不同的G蛋白，磷脂酶C，蛋白激酶C，钙调蛋白，促分裂原活化蛋白激酶，以及与细胞骨架有关的分子，其保持TJ在上皮的整个寿命中对生理要求和局部条件（特别是对Ca 2+依赖性细胞-细胞接触）敏感。
The tight junction (TJ) was first noticed through its ability to control permeation across the paracellular route, but the homologies of its molecular components with peptides that participate in tumor suppression, nuclear addressing, and cell proliferation indicate that it may be involved in many other fundamental functions. TJs are formed by a dozen molecular species that assemble through PDZ and other protein-protein clustering promoting sequences, in response to the activation of E-cadherin. The TJ occupies a highly specific position between the apical and the basolateral domains. Its first molecular components seem to be delivered to such a position by addressing signals in their molecule and, once anchored, serve as a clustering nucleus for further TJ-associated molecules. Although in mature epithelial cells TJs and E-cadherin do not colocalize, a complex chain of reactions goes from one to the other that involves alpha-, beta-, and gamma-catenins, two different G proteins, phospholipase C, protein kinase C, calmodulin, mitogen-activated protein kinase, and molecules pertaining to the cytoskeleton, which keep the TJ sensitive to physiological requirements and local conditions (notably to Ca2+-dependent cell-cell contacts) throughout the life of the epithelium.