Wakamatsu Kotaro, Ogita Hisakazu, Okabe Noriko, Irie Kenji, Tanaka-Okamoto Miki, Ishizaki Hiroyuki, Ishida-Yamamoto Akemi, Iizuka Hajime, Miyoshi Jun, Takai Yoshimi
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
J Biol Chem. 2007 Jun 22;282(25):18173-18181. doi: 10.1074/jbc.M611159200. Epub 2007 Apr 30.
Nectin is an immunoglobulin-like cell-cell adhesion molecule, which plays essential roles in the initial step of formation of adherens junctions and tight junctions. We demonstrate here the role of nectin-1 in the epidermis using nectin-1-/- mice. Newborn nectin-1-/- pups showed shiny and slightly reddish skin; the amount of loricrin, one of the differentiation markers and also a major component of cornified cell envelopes, was markedly reduced in the epidermis of nectin-1-/- mice. The amounts of repetin and SPRRP, other components of cornified cell envelopes, were markedly elevated probably due to a compensatory mechanism to overcome the impaired expression of loricrin. However, cornified cells from nectin-1-/- mice were sensitive to mechanical stress. Moreover, Ca2+-induced activation of ERK through Rap1 and expression of loricrin were reduced in primary cultured nectin-1-/- keratinocytes; in turn, the inhibition of ERK activation reduced the amount of loricrin in wild-type keratinocytes. These results indicate that nectin-1 plays a key role in the expression of loricrin in the epidermis.
连接蛋白是一种免疫球蛋白样细胞间黏附分子，在黏着连接和紧密连接形成的起始步骤中发挥着重要作用。我们在此利用连接蛋白-1基因敲除小鼠证明了连接蛋白-1在表皮中的作用。新生的连接蛋白-1基因敲除幼崽皮肤发亮且略带红色；在连接蛋白-1基因敲除小鼠的表皮中，一种分化标志物且也是角质化细胞包膜主要成分的兜甲蛋白的含量显著降低。角质化细胞包膜的其他成分，如重复蛋白和富含脯氨酸的小表皮相关蛋白的含量可能由于一种补偿机制而显著升高，以克服兜甲蛋白表达受损的情况。然而，来自连接蛋白-1基因敲除小鼠的角质化细胞对机械应力敏感。此外，在原代培养的连接蛋白-1基因敲除角质形成细胞中，通过Rap1的Ca2+诱导的细胞外信号调节激酶（ERK）激活以及兜甲蛋白的表达降低；反过来，抑制ERK激活会降低野生型角质形成细胞中兜甲蛋白的含量。这些结果表明，连接蛋白-1在表皮中兜甲蛋白的表达中起关键作用。
