Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases

The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked...

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Main Authors:	Van Campenhout, Claude A., Eitelhuber, Andrea, Gloeckner, Christian J., Giallonardo, Patrizia, Gegg, Moritz, Oller, Heide, Grant, Seth G.N., Krappmann, Daniel, Ueffing, Marius, Lickert, Heiko
Format:	Online
Language:	English
Published:	Cell Press 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452538/

id	pubmed-4452538
recordtype	oai_dc
spelling	pubmed-44525382015-06-03 Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases Van Campenhout, Claude A. Eitelhuber, Andrea Gloeckner, Christian J. Giallonardo, Patrizia Gegg, Moritz Oller, Heide Grant, Seth G.N. Krappmann, Daniel Ueffing, Marius Lickert, Heiko Article The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation. Cell Press 2011-09-13 /pmc/articles/PMC4452538/ /pubmed/21920314 http://dx.doi.org/10.1016/j.devcel.2011.08.003 Text en © 2011 Elsevier Inc. All rights reserved.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Van Campenhout, Claude A. Eitelhuber, Andrea Gloeckner, Christian J. Giallonardo, Patrizia Gegg, Moritz Oller, Heide Grant, Seth G.N. Krappmann, Daniel Ueffing, Marius Lickert, Heiko
spellingShingle	Van Campenhout, Claude A. Eitelhuber, Andrea Gloeckner, Christian J. Giallonardo, Patrizia Gegg, Moritz Oller, Heide Grant, Seth G.N. Krappmann, Daniel Ueffing, Marius Lickert, Heiko Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
author_facet	Van Campenhout, Claude A. Eitelhuber, Andrea Gloeckner, Christian J. Giallonardo, Patrizia Gegg, Moritz Oller, Heide Grant, Seth G.N. Krappmann, Daniel Ueffing, Marius Lickert, Heiko
author_sort	Van Campenhout, Claude A.
title	Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
title_short	Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
title_full	Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
title_fullStr	Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
title_full_unstemmed	Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases
title_sort	dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases
description	The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation.
publisher	Cell Press
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452538/
_version_	1613230757460836352

Dlg3 Trafficking and Apical Tight Junction Formation Is Regulated by Nedd4 and Nedd4-2 E3 Ubiquitin Ligases

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