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
- 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
- The laminin binding α3 and α6 integrins cooperate to promote epithelial cell adhesion and growth.
- Authors: Yazlovitskaya EM, Viquez OM, Tu T, De Arcangelis A, Georges-Labouesse E, Sonnenberg A, Pozzi A, Zent R
- Issue date: 2019 Apr
- Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration.
- Authors: Yebra M, Montgomery AM, Diaferia GR, Kaido T, Silletti S, Perez B, Just ML, Hildbrand S, Hurford R, Florkiewicz E, Tessier-Lavigne M, Cirulli V
- Issue date: 2003 Nov
- Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5alpha/beta.
- Authors: Hotta A, Kawakatsu T, Nakatani T, Sato T, Matsui C, Sukezane T, Akagi T, Hamaji T, Grigoriev I, Akhmanova A, Takai Y, Mimori-Kiyosue Y
- Issue date: 2010 May 31
- 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