Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Institute of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
PLoS One. 2020 Mar 12;15(3):e0230380. doi: 10.1371/journal.pone.0230380. eCollection 2020.
Epidermal morphogenesis and hair follicle (HF) development depend on the ability of keratinocytes to adhere to the basement membrane (BM) and migrate along the extracellular matrix. Integrins are cell-matrix receptors that control keratinocyte adhesion and migration, and are recognized as major regulators of epidermal homeostasis. How integrins regulate the behavior of keratinocytes during epidermal morphogenesis remains insufficiently understood. Here, we show that α-parvin (α-pv), a focal adhesion protein that couples integrins to actin cytoskeleton, is indispensable for epidermal morphogenesis and HF development. Inactivation of the murine α-pv gene in basal keratinocytes results in keratinocyte-BM detachment, epidermal thickening, ectopic keratinocyte proliferation and altered actin cytoskeleton polarization. In vitro, α-pv-null keratinocytes display reduced adhesion to BM matrix components, aberrant spreading and stress fibers formation, and impaired directed migration. Together, our data demonstrate that α-pv controls epidermal homeostasis by facilitating integrin-mediated adhesion and actin cytoskeleton organization in keratinocytes.
表皮形态发生和毛囊 (HF) 发育依赖于角蛋白细胞黏附基底膜 (BM) 和沿细胞外基质迁移的能力。整合素是细胞基质受体,可控制角蛋白细胞黏附和迁移,并被认为是表皮稳态的主要调节剂。整合素如何调节表皮形态发生过程中角蛋白细胞的行为尚不清楚。在这里,我们表明α-辅肌动蛋白 (α-pv),一种将整合素与肌动蛋白细胞骨架偶联的黏着斑蛋白,对角蛋白细胞表皮形态发生和 HF 发育是必不可少的。在基底角蛋白细胞中敲除小鼠α-pv 基因会导致角蛋白细胞与 BM 分离、表皮变厚、角蛋白细胞异常增殖和细胞骨架极化改变。在体外,α-pv 缺失的角蛋白细胞显示对 BM 基质成分的黏附减少、异常扩展和应力纤维形成以及定向迁移受损。总之,我们的数据表明,α-pv 通过促进角蛋白细胞中整合素介导的黏附和肌动蛋白细胞骨架组织来控制表皮稳态。