Tanaka Hiroo, Tamura Atsushi, Suzuki Koya, Tsukita Sachiko
Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan.
Ann N Y Acad Sci. 2017 Oct;1405(1):44-52. doi: 10.1111/nyas.13438. Epub 2017 Sep 4.
The claudins are a family of membrane proteins with at least 27 members in humans and mice. The extracellular regions of claudin proteins play essential roles in cell-cell adhesion and the paracellular barrier functions of tight junctions (TJs) in epithelial cell sheets. Furthermore, the extracellular regions of some claudins function as paracellular channels in the paracellular barrier that allow the selective passage of water, ions, and/or small organic solutes across the TJ in the extracellular space. Structural analyses have revealed a common framework of transmembrane, cytoplasmic, and extracellular regions among the claudin-based paracellular barriers and paracellular channels; however, differences in the claudins' extracellular regions, such as their charges and conformations, determine their properties. Among the biological systems that involve fluid flow and metabolism, it is noted that hepatic bile flow, renal Na reabsorption, and intestinal nutrient absorption are dynamically regulated via site-specific distributions of paracellular channel-forming claudins in tissue. Here, we focus on how site-specific distributions of claudin-2- and claudin-15-based paracellular channels drive their organ-specific functions in the liver, kidney, and intestine.
紧密连接蛋白是一类膜蛋白家族，在人类和小鼠中至少有27个成员。紧密连接蛋白的细胞外区域在上皮细胞层中细胞间黏附以及紧密连接（TJ）的细胞旁屏障功能中发挥着重要作用。此外，一些紧密连接蛋白的细胞外区域在细胞旁屏障中作为细胞旁通道，允许水、离子和/或小有机溶质在细胞外空间中选择性地穿过紧密连接。结构分析揭示了基于紧密连接蛋白的细胞旁屏障和细胞旁通道中跨膜、细胞质和细胞外区域的共同框架；然而，紧密连接蛋白细胞外区域的差异，如它们的电荷和构象，决定了它们的特性。在涉及流体流动和代谢的生物系统中，值得注意的是，肝胆汁流动、肾钠重吸收和肠道营养吸收通过组织中形成细胞旁通道的紧密连接蛋白的位点特异性分布受到动态调节。在这里，我们关注基于紧密连接蛋白-2和紧密连接蛋白-15的细胞旁通道的位点特异性分布如何驱动它们在肝脏、肾脏和肠道中的器官特异性功能。
