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

Dev. Cell 21, 479-491 (2011)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Zeitschrift Developmental Cell
Quellenangaben Band: 21, Heft: 3, Seiten: 479-491 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
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
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
Stem Cell and Neuroscience
PSP-Element(e) G-501900-231
G-502300-001
G-509800-002
G-505700-001
G-500890-001
Scopus ID 80052776738
PubMed ID 21920314
Erfassungsdatum 2011-09-21