Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes which provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes locally regulate keratin dynamics in addition to binding pre-assembled filaments. Ndel1 is a desmosome-associated protein in the differentiated epidermis, though its function at these structures has not been examined. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 was necessary for robust desmosome-keratin association and sufficient to reorganize keratins at distinct cellular sites. Lis1, a Ndel1 binding protein, was required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identifies Ndel1 as a desmosome-associated protein which promotes local assembly/reorganization of keratin filaments and is essential for robust desmosome formation.

角蛋白中间丝形成动态聚合物网络，其组织方式取决于细胞类型、细胞周期阶段和细胞状态。在表皮的分化细胞中，它们由桥粒组织，细胞-细胞粘附复合物为该组织提供必要的机械完整性。尽管如此，我们对角蛋白组织是如何被控制的以及桥粒是否除了结合预组装的细丝外还可以局部调节角蛋白动力学知之甚少。Ndel1 是分化表皮中的桥粒相关蛋白，尽管尚未检查其在这些结构中的功能。在这里，我们表明 Ndel1 通过在所有中间丝蛋白中保守的基序直接与角蛋白亚基结合。更远，Ndel1 是健壮的桥粒-角蛋白结合所必需的，并且足以在不同的细胞位点重组角蛋白。Lis1，一种 Ndel1 结合蛋白，是 Ndel1 桥粒定位所必需的，但不是因为它对角蛋白丝的影响。最后，我们使用小鼠遗传学来证明 Ndel1 的缺失会导致表皮中的桥粒缺陷。因此，我们的数据将 Ndel1 鉴定为一种桥粒相关蛋白，它促进角蛋白丝的局部组装/重组，对于稳健的桥粒形成至关重要。