PMID:21844209

Citation	Sumigray, KD, Chen, H and Lechler, T (2011) Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J. Cell Biol. 194:631-42
Abstract	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.
Links	PubMed PMC3160577 Online version:10.1083/jcb.201104009
Keywords	1-Alkyl-2-acetylglycerophosphocholine Esterase/deficiency; 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics; 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism; Animals; Carrier Proteins/metabolism; Cell Differentiation; Cell Proliferation; Cells, Cultured; Desmoplakins/deficiency; Desmoplakins/genetics; Desmosomes/metabolism; Epidermis/embryology; Epidermis/metabolism; Fluorescent Antibody Technique; Keratinocytes/metabolism; Mice; Mice, Knockout; Microtubule-Associated Proteins/deficiency; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Microtubules/metabolism; Permeability; Protein Transport; Recombinant Fusion Proteins/metabolism; Transfection; alpha Catenin/deficiency; alpha Catenin/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:LIS1		GO:0043622: cortical microtubule organization	ECO:0000315:		P		Figure 4	complete CACAO 7259
MOUSE:LIS1		GO:0002934: desmosome organization	ECO:0000315:		P		Figure 6	complete CACAO 7297
MOUSE:LIS1	involved_in	GO:0043622: cortical microtubule organization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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