Ingestion of Food Particles Regulates the Mechanosensing Misshapen-Yorkie Pathway in Drosophila Intestinal Growth

• Published in: Developmental cell Vol. 45; no. 4; pp. 433 - 449.e6
• Main Authors: Li, Qi, Nirala, Niraj K., Nie, Yingchao, Chen, Hsi-Ju, Ostroff, Gary, Mao, Junhao, Wang, Qi, Xu, Lan, Ip, Y. Tony
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-05-2018
• Subjects: Adaptation, Physiological; Animals; Cell Membrane - metabolism; Digestion; Drosophila; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Intestinal Absorption; Intestinal Mucosa - metabolism; intestine; Intestines - growth & development; kinases; Male; mechanosensing; Mechanotransduction, Cellular; membrane; Misshapen; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction; stem cells; Tao; Trans-Activators - genetics; Trans-Activators - metabolism; Warts; Yeasts - metabolism; Yorkie; Warts; stem cells; mechanosensing; intestine; kinases; membrane; Tao; Drosophila; Misshapen; Yorkie
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2018.04.014

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.
•Ingested particles expand the gut and reduce Misshapen membrane association•Mechanical properties change Misshapen membrane association and phosphorylation•Reduced membrane association of Misshapen decreases its T194 phosphorylation by Tao•Misshapen T194 phosphorylation is a control switch for regulating Warts-Yorkie
Yeast is a natural food source for fruit flies, and accumulation of yeast particles in their midgut causes expansion of the gut tube. Li et al. show that such expansion triggers a mechanosensing mechanism leading to the relief of inhibition of Yorkie-mediated tissue growth by the upstream kinase Misshapen.