Schlüter Holger, Moll Ingrid, Wolburg Hartwig, Franke Werner W
Division of Cell Biology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Eur J Cell Biol. 2007 Dec;86(11-12):645-55. doi: 10.1016/j.ejcb.2007.01.001. Epub 2007 Feb 8.
In stratified squamous epithelia constituent proteins of tight junctions (TJs) are not restricted to the zonula occludens-related structures of the uppermost living cell layer such as the stratum granulosum of the epidermis but TJ membrane proteins such as occludin and certain members of the claudin family as well as TJ plaque proteins, notably cingulin and protein ZO-1, have also been identified by immunofluorescence and immunoelectron microscopy in more basal layers where they form special cell-cell-connecting structures such as the "lamellated" and the "sandwich" junctions. In the present study, we describe another TJ protein-containing structure, the very small puncta occludentia ("stud junctions"), as the smallest identifiable TJ-like unit that occurs in most, perhaps all strata. We have also determined the specific distributions of TJ proteins in the cell layers of squamous cell metaplasias of the human bronchial tract. Moreover, we show that the occludin-related tetraspanin protein tricellulin-alpha connects and seals the membranes of adjacent "three corner" cell structures of the uppermost layer in keratinocytes growing in culture. We hypothesize the possible occurrence of tricellulin-beta in more basal cell layers of keratinocyte cultures and the general occurrence of different tricellulin splice forms in stratified epithelia in situ, and discuss the possible functions of TJ proteins in stratified epithelia and tumors derived therefrom.
在复层鳞状上皮中,紧密连接(TJ)的组成蛋白并不局限于最上层活细胞层的紧密连接相关结构,如表皮的颗粒层,但是通过免疫荧光和免疫电子显微镜在更基底的细胞层中也鉴定出了TJ膜蛋白,如闭合蛋白和某些紧密连接蛋白家族成员,以及TJ斑蛋白,特别是cingulin和蛋白ZO-1,它们在这些细胞层中形成特殊的细胞间连接结构,如“板层状”和“三明治”连接。在本研究中,我们描述了另一种含有TJ蛋白的结构,即非常小的封闭斑(“纽扣状连接”),它是在大多数,可能是所有细胞层中出现的最小可识别的TJ样单位。我们还确定了TJ蛋白在人支气管鳞状上皮化生细胞层中的具体分布。此外,我们表明,与闭合蛋白相关的四跨膜蛋白tricellulin-α连接并封闭了培养的角质形成细胞最上层相邻“三角”细胞结构的膜。我们推测tricellulin-β可能存在于角质形成细胞培养物的更基底细胞层中,并且原位复层上皮中普遍存在不同的tricellulin剪接形式,并讨论了TJ蛋白在复层上皮及其衍生肿瘤中的可能功能。