ENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes
ENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes
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ENKD1通过调节基底角质形成细胞的纺锤体方向促进表皮分层
DOI：
10.1038/s41418-022-00958-5
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发表时间：
2022
影响因子：
12.4
通讯作者：
Zhou Jun
中科院分区：
文献类型：
--
作者：
Zhong Tao;Wu Xiaofan;Xie Wei;Luo Xiangrui;Song Ting;Sun Shuang;Luo Youguang;Li Dengwen;Liu Min;Xie Songbo;Zhou Jun
表皮的分层对于皮肤的屏障功能是必不可少的。然而，表皮分层的分子机制尚未完全了解。在此，我们证明了含恩库蛋白结构域的蛋白1（ENKD 1）通过调节基底角质形成细胞的细胞分裂方向来促进表皮分层。Enkd 1基因敲除小鼠的表皮比野生型小鼠薄，这是由于通过不对称分裂从基底角质形成细胞产生的基底上细胞减少。ENKD 1的缺失损害了培养细胞中有丝分裂纺锤体的正确方向并延迟了有丝分裂进程。机制研究进一步揭示ENKD 1是一种新的微管结合蛋白，可促进星形微管的稳定性。引入ENKD 1的微管结合结构域可以在很大程度上挽救ENKD 1缺失细胞中的纺锤体取向缺陷。这些发现确立了ENKD 1作为星形微管稳定性和纺锤体取向的关键调节剂，其刺激哺乳动物细胞中的表皮分层。
Stratification of the epidermis is essential for the barrier function of the skin. However, the molecular mechanisms governing epidermal stratification are not fully understood. Herein, we demonstrate that enkurin domain-containing protein 1 (ENKD1) contributes to epidermal stratification by modulating the cell-division orientation of basal keratinocytes. The epidermis ofEnkd1knockout mice is thinner than that of wild-type mice due to reduced generation of suprabasal cells from basal keratinocytes through asymmetric division. Depletion of ENKD1 impairs proper orientation of the mitotic spindle and delays mitotic progression in cultured cells. Mechanistic investigation further reveals that ENKD1 is a novel microtubule-binding protein that promotes the stability of astral microtubules. Introduction of the microtubule-binding domain of ENKD1 can largely rescue the spindle orientation defects in ENKD1-depleted cells. These findings establish ENKD1 as a critical regulator of astral microtubule stability and spindle orientation that stimulates epidermal stratification in mammalian cells.