Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
J Cell Biol. 2011 Aug 22;194(4):631-42. doi: 10.1083/jcb.201104009. Epub 2011 Aug 15.
Desmosomes are cell-cell adhesion structures that integrate cytoskeletal networks. In addition to binding intermediate filaments, the desmosomal protein desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this paper, we identify a specific subset of centrosomal proteins that are recruited to the cell cortex by DP upon epidermal differentiation. These include Lis1 and Ndel1, which are centrosomal proteins that regulate microtubule organization and anchoring in other cell types. This recruitment was mediated by a region of DP specific to a single isoform, DPI. Furthermore, we demonstrate that the epidermal-specific loss of Lis1 results in dramatic defects in microtubule reorganization. Lis1 ablation also causes desmosomal defects, characterized by decreased levels of desmosomal components, decreased attachment of keratin filaments, and increased turnover of desmosomal proteins at the cell cortex. This contributes to loss of epidermal barrier activity, resulting in completely penetrant perinatal lethality. This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function.
桥粒是整合细胞骨架网络的细胞间黏附结构。除了结合中间丝外，桥粒蛋白桥粒斑蛋白（DP）还调节表皮中的微管重组。在本文中，我们鉴定出一组特定的中心体蛋白，这些蛋白在表皮分化时被 DP 募集到细胞皮质。其中包括在其他细胞类型中调节微管组织和锚定的中心体蛋白 Lis1 和 Ndel1。这种募集是由 DP 特有的一个单一异构体 DPI 的区域介导的。此外，我们证明表皮特异性的 Lis1 缺失会导致微管重组的严重缺陷。Lis1 缺失还会导致桥粒缺陷，表现为桥粒成分水平降低、角蛋白丝附着减少以及细胞皮质桥粒蛋白周转增加。这导致表皮屏障活性丧失，导致完全穿透性围产期致死性。这项工作揭示了控制皮质微管组织的必需桥粒相关成分，以及中心体蛋白在表皮功能中的意外作用。
