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MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

Steed, E; Elbediwy, A; Vacca, B; Dupasquier, S; Hemkemeyer, SA; Suddason, T; Costa, AC; ... Matter, K; + view all (2014) MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival. Journal of Cell Biology , 204 (5) 821 -838. 10.1083/jcb.201304115. Green open access

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Abstract

MarvelD3 is a transmembrane component of tight junctions, but there is little evidence for a direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, the transmembrane components that link the junction to such signaling pathways are not well understood. In this paper, we show that MarvelD3 is a dynamic junctional regulator of the MEKK1-c-Jun NH2-terminal kinase (JNK) pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in increased cell migration and proliferation, whereas reexpression in a metastatic tumor cell line inhibited migration, proliferation, and in vivo tumor formation. Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation and inhibition of JNK-regulated transcriptional mechanisms. Interplay between MarvelD3 internalization and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissociation and cell death in MarvelD3-depleted cells. MarvelD3 thus couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival.

Type: Article
Title: MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.201304115
Publisher version: http://dx.doi.org/10.1083/jcb.201304115
Language: English
Additional information: This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months (On 01/09/2014) it 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
URI: https://discovery.ucl.ac.uk/id/eprint/1421175
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