350 Chromatin remodelling ATFase Lsh maintains DNA methylation at constitutive heterochromatin and prevents activation of silent transposable elements in epidermal keratinocytes

Abstract

Keratin filaments are essential for the mechanical strength of the epidermis. This function requires their attachment to cell-cell adhesion structures called desmosomes. While we know the molecular basis of this attachment, whether and how keratin filament dynamics are controlled by the desmosome remains unknown. We identified the paralogs Ndel1 and Nde1 as desmosome-associated proteins whose loss in the epidermis resulted in disruption of keratin organization and desmosomal defects. We demonstrated that Ndel1 and Nde1 bind directly to keratin subunits through a conserved intermediate filament consensus motif but do not bind to assembled filaments. Targeting Ndel1 to the mitochondria resulted in reorganization of the keratin network around these organelles. Finally, we demonstrated that the binding partner of Ndel1/Nde1, Lis1, is necessary for their proper localization to the desmosomes but not for keratin filament assembly. Our results demonstrate that Ndel1 and Nde1 promote the local assembly of keratin at the desmosomes and thus are important for cell adhesion and epidermal function. ABSTRACTS | Epidermal Structure and Barrier Function