title: An integrin-ILK-microtubule network orients cell polarity and lumen formation in glandular epithelium.
abstract: The extracellular matrix has a crucial role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues; however, the underlying mechanisms remain elusive. By using Cre–Lox deletion we show that β1 integrins are required for normal mammary gland morphogenesis and lumen formation, both in vivo and in a three-dimensional primary culture model in which epithelial cells directly contact a basement membrane. Downstream of basement membrane β1 integrins, Rac1 is not involved; however, ILK is needed to polarize microtubule plus ends at the basolateral membrane and disrupting each of these components prevents lumen formation. The integrin–microtubule axis is necessary for the endocytic removal of apical proteins from the basement-membrane–cell interface and for internal Golgi positioning. We propose that this integrin signalling network controls the delivery of apical components to the correct surface and thereby governs the orientation of polarity and development of lumens.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M139PT, UK. nasreen.akhtar@manchester.ac.uk
authors.forename: Nasreen
authors.initials: N
authors.lastname: Akhtar
authors.forename: Charles H
authors.initials: CH
authors.lastname: Streuli
mesh_terms: D000818:Animals; D017209:Apoptosis; D018929:Cell Culture Techniques; D016764:Cell Polarity; D002478:Cells, Cultured; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009024:Morphogenesis; D009479:Neuropeptides / Q000378:metabolism; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D021601:trans-Golgi Network / Q000378:metabolism / Q000502:physiology; D000099200:Scaffold Protein ILK
chemical_list: D019012:Integrin beta1; D009479:Neuropeptides; D017346:Protein Serine-Threonine Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000099200:Scaffold Protein ILK; C484602:Rac1 protein, mouse