[HTML][HTML] Failure of epithelial tube maintenance causes hydrocephalus and renal cysts in Dlg5−/− mice

T Nechiporuk, TE Fernandez, V Vasioukhin - Developmental cell, 2007 - cell.com
T Nechiporuk, TE Fernandez, V Vasioukhin
Developmental cell, 2007cell.com
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 …
Summary
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.
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