Two Distinct Integrin-Mediated Mechanisms Contribute to Apical Lumen Formation in Epithelial Cells
MetadataShow full item record
AbstractBackground: 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 b1-integrins in epithelial polarization is well established but the significance of the accompanying a-subunits have not been analyzed in detail.
Principal Findings: 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) a2b1- and a6b4- integrins were required to establish a basal cue that depends on Rac1-activity and guides apico-basal cell polarization. 2) a3b1-integrins were implicated in positioning of mitotic spindles in cysts, a process that is essential for Cdc42-driven epithelial hollowing.
Significance: 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.
CitationPLoS One. 2011 May 6; 6(5):e19453
- alpha3beta1 and alpha6beta4 integrin receptors for laminin-5 are not essential for epidermal morphogenesis and homeostasis during skin development.
- Authors: DiPersio CM, van der Neut R, Georges-Labouesse E, Kreidberg JA, Sonnenberg A, Hynes RO
- Issue date: 2000 Sep
- Suppression of anoikis in human intestinal epithelial cells: differentiation state-selective roles of α2β1, α3β1, α5β1, and α6β4 integrins.
- Authors: Beauséjour M, Thibodeau S, Demers MJ, Bouchard V, Gauthier R, Beaulieu JF, Vachon PH
- Issue date: 2013 Dec 1
- Integrin expression and localization in normal MDCK cells and transformed MDCK cells lacking apical polarity.
- Authors: Schoenenberger CA, Zuk A, Zinkl GM, Kendall D, Matlin KS
- Issue date: 1994 Feb
- Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis.
- Authors: Chen D, Roberts R, Pohl M, Nigam S, Kreidberg J, Wang Z, Heino J, Ivaska J, Coffa S, Harris RC, Pozzi A, Zent R
- Issue date: 2004 Oct
- Regulation of epithelial cell surface polarity reversal by beta 1 integrins.
- Authors: Ojakian GK, Schwimmer R
- Issue date: 1994 Mar