Journal
DEVELOPMENTAL CELL
Volume 21, Issue 3, Pages 479-491Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2011.08.003
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Funding
- Helmholtz Society
- European Research Council
- German Research Foundation (DFG)
- EU [HEALTH-F5-2010-241955]
- German Federal Ministry of Education and Research [BMBF: DYNAMO, FKZ: 0315513A]
- Alexander von Humboldt Foundation
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The Drosophila Discs large (Dig) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dig 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 Dig 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 Dig family in basolateral epithelium formation.
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