Shifts in keratin isoform expression activate motility signals during wound healing,Developmental Cell

当前位置： X-MOL 学术 › Dev. Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Shifts in keratin isoform expression activate motility signals during wound healing
Developmental Cell ( IF 10.7 ) Pub Date : 2024-07-12 , DOI: 10.1016/j.devcel.2024.06.011
Benjamin A Nanes ₁ , Kushal Bhatt ₂ , Evgenia Azarova ₂ , Divya Rajendran ₂ , Sabahat Munawar ₂ , Tadamoto Isogai ₂ , Kevin M Dean ₂ , Gaudenz Danuser ₂

Affiliation

Keratin intermediate filaments confer structural stability to epithelial tissues, but the reason this simple mechanical function requires a protein family with 54 isoforms is not understood. During skin wound healing, a shift in keratin isoform expression alters the composition of keratin filaments. If and how this change modulates cellular functions that support epidermal remodeling remains unclear. We report an unexpected effect of keratin isoform variation on kinase signal transduction. Increased expression of wound-associated keratin 6A, but not of steady-state keratin 5, potentiated keratinocyte migration and wound closure without compromising mechanical stability by activating myosin motors to increase contractile force generation. These results substantially expand the functional repertoire of intermediate filaments from their canonical role as mechanical scaffolds to include roles as isoform-tuned signaling scaffolds that organize signal transduction cascades in space and time to influence epithelial cell state.

中文翻译：

角蛋白亚型表达的变化会激活伤口愈合过程中的运动信号

角蛋白中间丝赋予上皮组织结构稳定性，但这种简单的机械功能需要具有 54 种亚型的蛋白质家族的原因尚不清楚。在皮肤伤口愈合过程中，角蛋白亚型表达的变化会改变角蛋白丝的组成。这种变化是否以及如何调节支持表皮重塑的细胞功能尚不清楚。我们报道了角蛋白亚型变异对激酶信号转导的意外影响。伤口相关角蛋白 6A 的表达增加，但稳态角蛋白 5 的表达增加，通过激活肌球蛋白马达增加收缩力的产生，在不影响机械稳定性的情况下增强角质形成细胞迁移和伤口闭合。这些结果大大扩展了中间丝的功能库，从它们作为机械支架的经典作用扩展到包括作为亚型调谐信号支架的作用，这些支架在空间和时间上组织信号转导级联反应以影响上皮细胞状态。

更新日期：2024-07-12

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南