Ingestion of Food Particles Regulates the Mechanosensing Misshapen-Yorkie Pathway in Drosophila Intestinal Growth
Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology
Biochemical Phenomena, Metabolism, and Nutrition | Cell Biology | Cells | Developmental Biology | Digestive System | Enzymes and Coenzymes | Translational Medical Research
The intestinal epithelium has a high cell turnover rate and is an excellent system to study stem cell-mediated adaptive growth. In the Drosophila midgut, the Ste20 kinase Misshapen, which is distally related to Hippo, has a niche function to restrict intestinal stem cell activity. We show here that, under low growth conditions, Misshapen is localized near the cytoplasmic membrane, is phosphorylated at the threonine 194 by the upstream kinase Tao, and is more active toward Warts, which in turn inhibits Yorkie. Ingestion of yeast particles causes a midgut distention and a reduction of Misshapen membrane association and activity. Moreover, Misshapen phosphorylation is regulated by the stiffness of cell culture substrate, changing of actin cytoskeleton, and ingestion of inert particles. These results together suggest that dynamic membrane association and Tao phosphorylation of Misshapen are steps that link the mechanosensing of intestinal stretching after food particle ingestion to control adaptive growth.
Drosophila, Misshapen, Tao, Warts, Yorkie, intestine, kinases, mechanosensing, membrane, stem cells, UMCCTS funding
DOI of Published Version
Dev Cell. 2018 May 21;45(4):433-449.e6. doi: 10.1016/j.devcel.2018.04.014. Epub 2018 May 10. Link to article on publisher's site
Li, Qi; Nirala, Niraj K.; Nie, Yingchao; Chen, Hsi-Ju; Ostroff, Gary R.; Mao, Junhao; Wang, Qi; Xu, Lan; and Ip, Y. Tony, "Ingestion of Food Particles Regulates the Mechanosensing Misshapen-Yorkie Pathway in Drosophila Intestinal Growth" (2018). UMass Center for Clinical and Translational Science Supported Publications. 142.