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

Publication Type:

Journal Article

Source:

Developmental cell, Volume 13, Issue 3, p.338-50 (2007)

Keywords:

ADHERENS JUNCTIONS, Animals, Animals, Newborn, beta Catenin, Cadherins, Carrier Proteins, Cell Line, Cell Membrane, Cell Polarity, Cells, Cultured, Dogs, Electroporation, Epithelial Cells, Fibroblasts, Guanylate Kinase, Humans, Hydrocephalus, In Situ Hybridization, Kidney, Kinetics, Membrane Proteins, MICE, Mice, Knockout, Models, Biological, Polycystic Kidney Diseases, Qa-SNARE Proteins, Transfection

Abstract:

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.