Bewley Maria C, Tash Brian R, Tian Fang, Flanagan John M
Department of Biochemistry and Molecular Biology; Pennsylvania State University College of Medicine; Hershey, PA USA.
Renal Electrolyte and Hypertension Division; University of Pennsylvania; Philadelphia, PA USA.
Tissue Barriers. 2013 Jan 1;1(1):e23496. doi: 10.4161/tisb.23496.
Tight junctions (TJs) are protein complexes comprised of claudins, which anchor them in the membrane and numerous cytosolic scaffolding proteins including MAGI, MUPP1, cingulin and members of the Zonula Occludens (ZO) family. Originally, their main function was thought to be as a paracellular barrier. More recently, however, additional roles in signal transduction, differentiation and proliferation have been reported. Dysregulation is associated with a wide range of disease states, including diabetic retinopathy, irritable bowel disease and some cancers. ZO proteins and occludin form a protein complex that appears to act as a master regulator of TJ assembly/disassembly. Recent studies have highlighted the structural character of the primary ZO-1:occludin interaction and identified regions on occludin that control association and disassociation of TJ in a phosphorylation-dependent manner. We hypothesize that regions within ZO-1 in the so-called U5 and U6 regions behave in a similar manner.
紧密连接（TJs）是由紧密连接蛋白组成的蛋白质复合物，这些紧密连接蛋白将其锚定在膜上，还有众多胞质支架蛋白，包括膜相关鸟苷酸激酶反向蛋白（MAGI）、多 PDZ 域蛋白 1（MUPP1）、cingulin 以及紧密连接相关蛋白（ZO）家族成员。最初，它们的主要功能被认为是作为细胞旁屏障。然而，最近有报道称它们在信号转导、分化和增殖中还具有其他作用。功能失调与多种疾病状态相关，包括糖尿病视网膜病变、肠易激综合征和一些癌症。ZO 蛋白和闭合蛋白形成一种蛋白质复合物，似乎充当紧密连接组装/拆卸的主要调节因子。最近的研究突出了主要的 ZO - 1：闭合蛋白相互作用的结构特征，并确定了闭合蛋白上以磷酸化依赖方式控制紧密连接缔合和解离的区域。我们推测，所谓的 U5 和 U6 区域内的 ZO - 1 区域也有类似行为。
