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van Campenhout, C.A. ; Eitelhuber, A. ; Gloeckner, C.J. ; Giallonardo, P. ; Gegg, M. ; Oller, H. ; Grant, S.G.* ; Krappmann, D. ; Ueffing, M. ; Lickert, H.

Dlg3 trafficking and apical tight junction formation is regulated by Nedd4 and Nedd4-2 E3 ubiquitin ligases.

Dev. Cell 21, 479-491 (2011)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 21, Issue: 3, Pages: 479-491 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Research Unit Signaling and Translation (SAT)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Stem Cell Research (ISF)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
Stem Cell and Neuroscience
PSP Element(s) G-501900-231
G-502300-001
G-509800-002
G-505700-001
G-500890-001
DOI 10.1016/j.devcel.2011.08.003
Scopus ID 80052776738
PubMed ID 21920314
Erfassungsdatum 2011-09-21
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