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Review
. 2014 Aug 1;127(Pt 15):3217-25.
doi: 10.1242/jcs.146142. Epub 2014 Jul 2.

Integrins and epithelial cell polarity

Jessica L Lee  1 , Charles H Streuli  2
Affiliations
Review

Integrins and epithelial cell polarity

Jessica L Lee et al. J Cell Sci. .

Abstract

Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity.

Keywords: +TIPS; Basement membrane; Breast; Endocytosis; Epithelium; ILK; Integrin; Laminin; Mammary; Microtubule; Polarity.

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Figures

Fig. 1.
Fig. 1.
A cascade of integrin signalling establishes polarity. (A) Integrin-binding to extracellular collagen initiates a Rac1-dependent pathway that stimulates the production of a basal actin cortex through IRSp53. (B) Laminin is assembled into a basement membrane in a Rac1-depdendent mechanism. In the Drosophila egg chamber, the ER exit site factor Tango1 is required for basal secretion, while Rab10 and the GEF Crag restrict basement membrane secretion and assembly basally. (C) Integrin binding to extracellular laminin that is organised into a basement membrane induces polarity signalling through the scaffolding factor ILK. The Par3 complex forms independently, but basal ECM–integrin positioning is needed to orientate the apical surface.
Fig. 2.
Fig. 2.
Microtubules polarise spreading cells for migration and epithelial cells in the apical–basal orientation. (A) In spreading and migrating cells, microtubules are orientated from the centrosome towards the periphery (1). Plus-end-directed microtubule motors transport cargoes to the leading edge (2). Phosphorylation of CLASP1 and/or CLASP2 controls the extent of their association with microtubule plus ends (3). The Par3–aPKC–TIAM1 complex stabilises microtubules at the leading edge to allow persistent migration (4). (B) In polarised epithelia, non-centrosomal microtubules are orientated along the apical–basal axis (1). Plus-end-directed motors transport adhesion proteins and other cargoes to the basal surface (2). Known and possible interactions linking integrins with microtubules (3). Par1b and the microtubule crosslinker MTCL1 determine the balance between stable and dynamic non-centrosomal apical–basal microtubules (4).
Fig. 3.
Fig. 3.
Trafficking events required to establish basal membrane identity. Several trafficking events are involved in establishing basolateral membrane polarity. During polarity inversion, apical components such as tight junction proteins are trafficked away from the apical surface in a β1-integrin-dependent manner to create a basally defined surface (1). Rab-dependent endosomal trafficking is also required to transcytose apical components away from the basal surface in order to establish epithelial polarity (2). Caveolae are delivered to the basolateral surface in an ILK-dependent mechanism to establish basal caveolae signalling platforms that provide a distinct lipid microenvironment at the basolateral membrane (3). Clathrin-dependent trafficking is implicated in delivering Golgi-derived basolateral membrane proteins, such as the transferrin and LDL receptors, to the basal membrane (4). Radil sequestration and transport by Klf14, a component of plus-end-directed microtubule motors, regulates Rap1-mediated integrin signalling, which might control polarity originating at the basolateral membrane (5).
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Comment in

  • ERM proteins at a glance.
    McClatchey AI. McClatchey AI. J Cell Sci. 2014 Aug 1;127(Pt 15):3199-204. doi: 10.1242/jcs.098343. Epub 2014 Jun 20. J Cell Sci. 2014. PMID: 24951115 Free PMC article.

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