Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Dermatology, Nippon Medical School, Tokyo, Japan.
Exp Dermatol. 2021 Jan;30(1):62-67. doi: 10.1111/exd.14196. Epub 2020 Oct 6.
Type XVII collagen (COL17) is a transmembrane protein expressed in the basal epidermis. COL17 serves as a niche for epidermal stem cells, and although its reduction has been implicated in altering cell polarity and ageing of the epidermis, it is unknown how COL17 affects epidermal cell polarity. Here, we uncovered COL17 as a binding partner of the aPKC-PAR complex, which is a key regulating factor of cell polarity. Immunoprecipitation-immunoblot assay and protein-protein binding assay revealed that COL17 interacts with aPKC and PAR3. COL17 deficiency or epidermis-specific aPKCλ deletion destabilized PAR3 distribution in the epidermis, while aPKCζ knockout did not. Asymmetrical cell division was pronounced in COL17-null neonatal paw epidermis. These results show that COL17 is pivotal for maintaining epidermal cell polarity. Our study highlights the previously unrecognized role of COL17 in the basal keratinocytes.
XVII 型胶原（COL17）是一种表达于基底层表皮的跨膜蛋白。COL17 作为表皮干细胞的龛位，虽然其减少已被牵连到改变细胞极性和表皮老化，但尚不清楚 COL17 如何影响表皮细胞极性。在这里，我们发现 COL17 是 aPKC-PAR 复合物的结合伴侣，aPKC-PAR 复合物是细胞极性的关键调节因子。免疫沉淀-免疫印迹分析和蛋白质-蛋白质结合分析表明，COL17 与 aPKC 和 PAR3 相互作用。COL17 缺失或表皮特异性 aPKCλ 缺失使 PAR3 在表皮中的分布不稳定，而 aPKCζ 敲除则不会。COL17 缺失的新生爪皮中不对称细胞分裂明显。这些结果表明 COL17 对维持表皮细胞极性至关重要。我们的研究强调了 COL17 在基底角质形成细胞中以前未被认识到的作用。
