Inagaki Maiko, Irie Kenji, Ishizaki Hiroyoshi, Tanaka-Okamoto Miki, Morimoto Koji, Inoue Eiji, Ohtsuka Toshihisa, Miyoshi Jun, Takai Yoshimi
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Development. 2005 Apr;132(7):1525-37. doi: 10.1242/dev.01697. Epub 2005 Feb 23.
Nectins are Ca2+-independent immunoglobulin-like cell-cell-adhesion molecules consisting of four members. Nectins homophilically and heterophilically trans-interact to form a variety of cell-cell junctions, including cadherin-based adherens junctions in epithelial cells and fibroblasts in culture, synaptic junctions in neurons, and Sertoli cell-spermatid junctions in the testis, in cooperation with, or independently of, cadherins. To further explore the function of nectins, we generated nectin 1-/- and nectin 3-/-)mice. Both nectin 1-/- and nectin 3-/- mice showed a virtually identical ocular phenotype, microphthalmia, accompanied by a separation of the apex-apex contact between the pigment and non-pigment cell layers of the ciliary epithelia. Immunofluorescence and immunoelectron microscopy revealed that nectin 1 and nectin 3, but not nectin 2, localized at the apex-apex junctions between the pigment and non-pigment cell layers of the ciliary epithelia. However, nectin 1-/- and nectin 3-/- mice showed no impairment of the apicolateral junctions between the pigment epithelia where nectin 1, nectin 2 and nectin 3 localized, or of the apicolateral junctions between the non-pigment epithelia where nectin 2 and nectin 3, but not nectin 1, localized. These results indicate that the heterophilic trans-interaction between nectin 1 and nectin 3 plays a sentinel role in establishing the apex-apex adhesion between the pigment and non-pigment cell layers of the ciliary epithelia that is essential for the morphogenesis of the ciliary body.
NECTIN 是一类不依赖钙离子的免疫球蛋白样细胞间黏附分子，由四个成员组成。NECTIN 可通过同源和异源反式相互作用，与钙黏蛋白协同或独立形成多种细胞间连接，包括培养的上皮细胞和成纤维细胞中基于钙黏蛋白的黏附连接、神经元中的突触连接以及睾丸中的支持细胞 - 精子细胞连接。为了进一步探究 NECTIN 的功能，我们培育了 Nectin 1 - / - 和 Nectin 3 - / - 小鼠。Nectin 1 - / - 和 Nectin 3 - / - 小鼠表现出几乎相同的眼部表型，即小眼症，同时伴有睫状体上皮色素细胞层和非色素细胞层之间顶端 - 顶端接触的分离。免疫荧光和免疫电子显微镜显示，NECTIN 1 和 NECTIN 3 定位于睫状体上皮色素细胞层和非色素细胞层之间的顶端 - 顶端连接处，而 NECTIN 2 则不然。然而，Nectin 1 - / - 和 Nectin 3 - / - 小鼠中，NECTIN 1、NECTIN 2 和 NECTIN 3 定位于其中的色素上皮细胞之间的顶端外侧连接，以及 NECTIN 2 和 NECTIN 3（而非 NECTIN 1）定位于其中的非色素上皮细胞之间的顶端外侧连接均未受损。这些结果表明，NECTIN 1 和 NECTIN 3 之间的异源反式相互作用在建立睫状体上皮色素细胞层和非色素细胞层之间的顶端 - 顶端黏附中起关键作用，而这种黏附对于睫状体的形态发生至关重要。
