Abstract：
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.
摘要：
角蛋白中间丝赋予上皮组织结构稳定性，但是，这种简单的机械功能需要一个具有54个同工型的蛋白质家族的原因尚不清楚。在皮肤伤口愈合期间，角蛋白同工型表达的变化改变了角蛋白细丝的组成。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。我们报道了角蛋白同工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，但不是稳态角蛋白5，通过激活肌球蛋白马达以增加收缩力的产生，增强了角质形成细胞的迁移和伤口闭合而不损害机械稳定性。这些结果实质上扩展了中间丝的功能库，从其作为机械支架的规范作用扩展到包括作为同工型调节的信号传导支架的作用，该信号传导支架在空间和时间上组织信号转导级联以影响上皮细胞状态。
