Dlg5 interacts with the TGF-β receptor and promotes its degradation

• Dlg5 interacts with both the TGF-β type I and type II receptors.
• Dlg5 colocalizes with TGF-β receptors at the plasma membrane.
• Dlg5 promotes TGF-β type I receptor degradation.
• These findings can explain how Dlg5 regulates TGF-β signaling.

Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase adaptor family of proteins and is involved in epithelial-to-mesenchymal transition via transforming growth factor-β (TGF-β) signaling. However, the mechanism underlying the regulation of TGF-β signaling is unclear. We show here that Dlg5 interacts and colocalizes with both TGF-β type I (TβRI) and type II (TβRII) receptors at the plasma membrane. TβRI activation is not required for this interaction. Furthermore, the overexpression of Dlg5 enhances the degradation of TβRI. Proteasome inhibitors inhibited this enhanced degradation. These results suggest that Dlg5 interacts with TβRs and promotes their degradation.

Structured summary of protein interactionsDLG5physically interacts with TβRII and TβRI by anti tag coimmunoprecipitation (View interaction)DLG5physically interacts with TβRII by anti tag coimmunoprecipitation (View interaction)TβRIphysically interacts with DLG5 by anti bait coimmunoprecipitation (View interaction)DLG5, TβRI and TβRIIcolocalize by fluorescence microscopy (View interaction)DLG5physically interacts with TβRI by anti tag coimmunoprecipitation (View interaction)