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

Claude A. Van Campenhout, Andrea Eitelhuber, Christian J. Gloeckner, Patrizia Giallonardo, Moritz Gegg, Heide Oller, Seth G. N. Grant, Daniel Krappmann, Marius Ueffing, Heiko Lickert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)479-491
Number of pages13
JournalDevelopmental Cell
Volume21
Issue number3
DOIs
Publication statusPublished - 13 Sept 2011

Keywords / Materials (for Non-textual outputs)

  • DROSOPHILA
  • POLARIZATION
  • NMDA RECEPTOR
  • SEC6/8 COMPLEX
  • PROTEIN PHOSPHATASE-1
  • MICE
  • EXOCYST COMPLEX
  • MAMMALIAN EPITHELIAL-CELLS
  • MOUSE EMBRYO
  • PLANAR POLARITY

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