Failure of epithelial tube maintenance causes hydrocephalus and renal cysts in Dlg5-/- mice

Dev Cell. 2007 Sep;13(3):338-50. doi: 10.1016/j.devcel.2007.07.017.


Epithelial tubes represent fundamental building blocks of metazoan organisms; however, the mechanisms responsible for their formation and maintenance are not well understood. Here, we show that the evolutionarily conserved coiled-coil MAGUK protein Dlg5 is required for epithelial tube maintenance in mammalian brain and kidneys. We demonstrate that Dlg5(-/-) mice develop fully penetrant hydrocephalus and kidney cysts caused by a deficiency in membrane delivery of cadherin-catenin adhesion complexes and loss of cell polarity. Dlg5 travels with cadherin-containing vesicles and binds to syntaxin 4, a t-SNARE protein that regulates fusion of transport vesicles with the lateral membrane domain. We propose that Dlg5 functions in plasma membrane delivery of cadherins by linking cadherin-containing transport vesicles with the t-SNARE targeting complex. These findings show that Dlg5 is causally involved in hydrocephalus and renal cysts and reveal that targeted membrane delivery of cadherin-catenin adhesion complexes is critical for cell polarity and epithelial tube maintenance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adherens Junctions / metabolism
  • Animals
  • Animals, Newborn
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Polarity
  • Cells, Cultured
  • Dogs
  • Electroporation
  • Epithelial Cells / metabolism
  • Fibroblasts / metabolism
  • Guanylate Kinases / genetics
  • Humans
  • Hydrocephalus / etiology*
  • Hydrocephalus / pathology
  • In Situ Hybridization
  • Kidney / cytology
  • Kinetics
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Polycystic Kidney Diseases / etiology*
  • Polycystic Kidney Diseases / pathology
  • Qa-SNARE Proteins / metabolism
  • Transfection
  • beta Catenin / metabolism


  • Cadherins
  • Carrier Proteins
  • Membrane Proteins
  • Qa-SNARE Proteins
  • beta Catenin
  • Dlg5 protein, mouse
  • Guanylate Kinases