2. Academic Validation
  3. ENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes

ENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes

  • Cell Death Differ. 2022 Sep;29(9):1719-1729. doi: 10.1038/s41418-022-00958-5.
Tao Zhong # 1,  Xiaofan Wu # 2,  Wei Xie 1,  Xiangrui Luo 1,  Ting Song 1,  Shuang Sun 1,  Youguang Luo 1,  Dengwen Li 2,  Min Liu 1,  Songbo Xie 3,  Jun Zhou 4 5
Affiliations

Affiliations

  • 1 College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China.
  • 2 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecology, Nankai University, Tianjin, 300071, China.
  • 3 College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China. xiesongbo@sdnu.edu.cn.
  • 4 College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China. junzhou@sdnu.edu.cn.
  • 5 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecology, Nankai University, Tianjin, 300071, China. junzhou@sdnu.edu.cn.
  • # Contributed equally.
PMID: 35197565 DOI: 10.1038/s41418-022-00958-5
Abstract

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 of Enkd1 knockout 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.

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