title: Two distinct integrin-mediated mechanisms contribute to apical lumen formation in epithelial cells.
abstract: BACKGROUND
  Formation of apical compartments underlies the morphogenesis of most epithelial organs during development. The extracellular matrix (ECM), particularly the basement membrane (BM), plays an important role in orienting the apico-basal polarity and thereby the positioning of apical lumens. Integrins have been recognized as essential mediators of matrix-derived polarity signals. The importance of β1-integrins in epithelial polarization is well established but the significance of the accompanying α-subunits have not been analyzed in detail.
  
  
  RESULTS
  Here we demonstrate that two distinct integrin-dependent pathways regulate formation of apical lumens to ensure robust apical membrane biogenesis under different microenvironmental conditions; 1) α2β1- and α6β4-integrins were required to establish a basal cue that depends on Rac1-activity and guides apico-basal cell polarization. 2) α3β1-integrins were implicated in positioning of mitotic spindles in cysts, a process that is essential for Cdc42-driven epithelial hollowing.
  
  
  CONCLUSIONS
  Identification of the separate processes driven by particular integrin receptors clarifies the functional hierarchies between the different integrins co-expressed in epithelial cells and provides valuable insight into the complexity of cell-ECM interactions thereby guiding future studies addressing the molecular basis of epithelial morphogenesis during development and disease.
authors.affiliation: Biocenter Oulu, Oulu Center for Cell-Matrix Research, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
authors.forename: Satu Marja
authors.initials: SM
authors.lastname: Myllymäki
authors.forename: Terhi Piritta
authors.initials: TP
authors.lastname: Teräväinen
authors.forename: Aki
authors.initials: A
authors.lastname: Manninen
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism*; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering
chemical_list: D038982:Integrin alpha2beta1; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D034741:RNA, Small Interfering