1. Regulation of YAP and Wnt signaling by the endosomal protein MAMDC4.
- Author
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Cox, Christopher M., Wu, Meng-Han, Padilla-Rodriguez, Marco, Blum, Isabella, Momtaz, Samina, Mitchell, Stefanie A. T., and Wilson, Jean M.
- Subjects
WNT signal transduction ,YAP signaling proteins ,INTESTINAL mucosa ,MEMBRANE proteins ,GENETIC transcription regulation ,HOMEOSTASIS - Abstract
Maintenance of the intestinal epithelium requires constant self-renewal and regeneration. Tight regulation of proliferation and differentiation of intestinal stem cells within the crypt region is critical to maintaining homeostasis. The transcriptional co-factors β-catenin and YAP are required for proliferation during normal homeostasis as well as intestinal regeneration after injury: aberrant signaling activity results in over proliferation and tumorigenesis. Although both YAP and β-catenin activity are controlled along canonical pathways, it is becoming increasingly clear that non-canonical regulation of these transcriptional regulators plays a role in fine tuning their activity. We have shown previously that MAMDC4 (Endotubin, AEGP), an integral membrane protein present in endosomes, regulates both YAP and β-catenin activity in kidney epithelial cells and in the developing intestinal epithelium. Here we show that MAMDC4 interacts with members of the signalosome and mediates cross-talk between YAP and β-catenin. Interestingly, this cross-talk occurs through a non-canonical pathway involving interactions between AMOT:YAP and AMOT:β-catenin. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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