| First Author | Guo Y | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32369015 | Mgi Jnum | J:290210 |
| Mgi Id | MGI:6442011 | Doi | 10.7554/eLife.53165 |
| Citation | Guo Y, et al. (2020) Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3sigma and YAP1. Elife 9:e53165 |
| abstractText | The intermediate filament protein keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at Krt14's codon 373 (C373A) exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in epidermis. A proteomics screen identified 14-3-3 as K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14 C373A keratinocytes. Residue C373 in K14, which is conserved in a subset of keratins, is revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in epidermis. |
