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Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation.

Zihni, C; Munro, PM; Elbediwy, A; Keep, NH; Terry, SJ; Harris, J; Balda, MS; (2014) Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation. The Journal of Cell Biology , 204 (1) 111 - 127. 10.1083/jcb.201304064. Green open access

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Abstract

Epithelial cells develop morphologically characteristic apical domains that are bordered by tight junctions, the apical-lateral border. Cdc42 and its effector complex Par6-atypical protein kinase c (aPKC) regulate multiple steps during epithelial differentiation, but the mechanisms that mediate process-specific activation of Cdc42 to drive apical morphogenesis and activate the transition from junction formation to apical differentiation are poorly understood. Using a small interfering RNA screen, we identify Dbl3 as a guanine nucleotide exchange factor that is recruited by ezrin to the apical membrane, that is enriched at a marginal zone apical to tight junctions, and that drives spatially restricted Cdc42 activation, promoting apical differentiation. Dbl3 depletion did not affect junction formation but did affect epithelial morphogenesis and brush border formation. Conversely, expression of active Dbl3 drove process-specific activation of the Par6-aPKC pathway, stimulating the transition from junction formation to apical differentiation and domain expansion, as well as the positioning of tight junctions. Thus, Dbl3 drives Cdc42 signaling at the apical margin to regulate morphogenesis, apical-lateral border positioning, and apical differentiation.

Type: Article
Title: Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.201304064
Publisher version: http://dx.doi.org/10.1083/jcb.201304064
Language: English
Additional information: Until July 6th 2014, this article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license (see http://www.rupress.org/terms). After July 6th 2014, this article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported) license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1417707
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