Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin β4 cytoplasmic domain

Autor: Chiara Murgia, Nancy Kim, Michael Dans, Howard T. Petrie, Pamela Blaikie, Filippo G. Giancotti
Rok vydání: 1998
Předmět:
Keratinocytes
Cytoplasm
Integrins
Duodenum
Microtubule-associated protein
Integrin
Cell Cycle Proteins
Junctional epidermolysis bullosa (medicine)
Basement Membrane
General Biochemistry
Genetics and Molecular Biology
Mice
Antigens
CD
Laminin
Cell Adhesion
medicine
Animals
Intestinal Mucosa
Cell adhesion
Molecular Biology
Cells
Cultured
Cytoskeleton
Pylorus
Sequence Deletion
Skin
Integrin alpha6beta4
Mice
Knockout
Basement membrane
General Immunology and Microbiology
biology
Integrin beta4
Cell adhesion molecule
Tumor Suppressor Proteins
General Neuroscience
Cell Cycle
Desmosomes
medicine.disease
Molecular biology
Cell biology
medicine.anatomical_structure
Antigens
Surface
biology.protein
Epidermolysis Bullosa
Junctional
Cell Adhesion Molecules
Microtubule-Associated Proteins
Cyclin-Dependent Kinase Inhibitor p27
Research Article
Zdroj: The EMBO Journal. 17:3940-3951
ISSN: 1460-2075
0261-4189
DOI: 10.1093/emboj/17.14.3940
Popis: The cytoplasmic domain of the integrin beta4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein Shc. To examine the significance of these interactions during development, we have generated mice carrying a targeted deletion of the beta4 cytoplasmic domain. Analysis of homozygous mutant mice indicates that the tail-less alpha6beta4 binds efficiently to laminin 5, but is unable to integrate with the cytoskeleton. Accordingly, these mice display extensive epidermal detachment at birth and die immmediately thereafter from a syndrome resembling the human disease junctional epidermolysis bullosa with pyloric atresia (PA-JEB). In addition, we find a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin is reduced, and post-mitotic enterocytes display increased levels of the cyclin-dependent kinase inhibitor p27(Kip). These findings indicate that the interactions mediated by the beta4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell-cycle control in the proliferative compartments of both stratified and simple epithelia.
Databáze: OpenAIRE
Externí odkaz: