Bunched and Madm Function Downstream of Tuberous Sclerosis Complex to Regulate the Growth of Intestinal Stem Cells in Drosophila
Year: 2015
Type: article
Abstract: The Drosophila adult midgut contains intestinal stem cells that support homeostasis and repair. We show here that the leucine zipper protein Bunched and the adaptor protein Madm are novel regulators of intestinal stem cells. MARCM mutant clonal analysis and cell type specific RNAi revealed that Bunched and Madm were required within intestinal stem cells for proliferation. Transgenic expression of a tagged Bunched showed a cytoplasmic localization in midgut precursors, and the addition of a nuclear localization signal to Bunched reduced its function to cooperate with Madm to increase intestinal stem cell proliferation. Furthermore, the elevated cell growth and 4EBP phosphorylation phenotypes induced by loss of Tuberous Sclerosis Complex or overexpression of Rheb were suppressed by the loss of Bunched or Madm. Therefore, while the mammalian homolog of Bunched, TSC-22, is able to regulate transcription and suppress cancer cell proliferation, our data suggest the model that Bunched and Madm functionally interact with the TOR pathway in the cytoplasm to regulate the growth and subsequent division of intestinal stem cells.
Source: Stem Cell Reviews and Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: National Science Foundation, University of Nevada, Las Vegas, National Institutes of Health, Center for Clinical and Translational Science, University of Massachusetts, Guangdong Province Introduction of Innovative R&D Team, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Integrative Organismal Systems, National Center for Advancing Translational Sciences
Awards: Homeostatic signaling in the Drosophila intestine, G2677314950, G2723925609, G3187650539, G3632648099, University of Massachusetts Center for Clinical and Translational Science, G5015477133, Conserved mechanisms in epithelial niche regulation of intestinal stem cells, Diabetes Endocrinology Research Center (DERC), Steroid-Dependent Changes in the Yorkie Interactome, TGF-beta family regulation of epithelial morphogenesis , G8518005984, G9000110905, Nevada IDeA Networks of Biomedical Research Excellence (INBRE)
OpenAlex ID: W1257374170