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  3. CFAP100 couples microtubule glutamylation to spindle pole integrity in keratinocytes to promote epidermal development

CFAP100 couples microtubule glutamylation to spindle pole integrity in keratinocytes to promote epidermal development

  • Nat Commun. 2025 Jul 1;16(1):5591. doi: 10.1038/s41467-025-60677-6.
Shuang Sun 1,  Zhaoying Wang 2,  Zhaoyang Xu 2,  Zhengfeng Wang 2,  Jia Sun 2,  Keke Li 2,  Min Liu 2,  Huijie Zhao 2,  Peiwei Liu 3,  Jun Zhou 4 5
Affiliations

Affiliations

  • 1 Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China. shuangsun2017@sdnu.edu.cn.
  • 2 Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.
  • 3 Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China. liupw@sdnu.edu.cn.
  • 4 Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China. junzhou@sdnu.edu.cn.
  • 5 Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. junzhou@sdnu.edu.cn.
PMID: 40593606 DOI: 10.1038/s41467-025-60677-6
Abstract

Despite the importance of keratinocytes in epidermal structure and function, the molecular mechanisms regulating the division of these cells remain poorly understood. Herein, we demonstrate an essential role for cilia and flagella associated protein 100 (CFAP100) in keratinocyte division. Cfap100-knockout mice display a thinner and transparent skin and an impaired epidermal barrier function. Depletion of CFAP100 in keratinocytes prolongs mitotic progression and compromises chromosome segregation. Molecular studies reveal that CFAP100 interacts with tubulin tyrosine ligase-like protein 13 (TTLL13) to maintain spindle pole integrity in dividing keratinocytes. Further analysis shows that CFAP100 recruits TTLL13 to the spindle pole to increase the glutamylation of spindle microtubules. Restoring microtubule glutamylation by overexpression of TTLL13 or depletion of cytosolic Carboxypeptidase 5 remarkably rescues the spindle pole defects in CFAP100-depleted cells. These findings thus identify CFAP100 as a central link to couple microtubule glutamylation to spindle pole integrity in keratinocytes to promote epidermal development.

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