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Publication : Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis.

First Author  Sumigray KD Year  2011
Journal  J Cell Biol Volume  194
Issue  4 Pages  631-42
PubMed ID  21844209 Mgi Jnum  J:176963
Mgi Id  MGI:5293247 Doi  10.1083/jcb.201104009
Citation  Sumigray KD, et al. (2011) Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J Cell Biol 194(4):631-42
abstractText  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.
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