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Dev Cell. 2018 May 21;45(4):433-449.e6. doi: 10.1016/j.devcel.2018.04.014. Epub 2018 May 10.

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

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3
Neuroscience Research Unit, Pfizer, Cambridge, MA 02139, USA.
4
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: tony.ip@umassmed.edu.

Abstract

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.

KEYWORDS:

Drosophila; Misshapen; Tao; Warts; Yorkie; intestine; kinases; mechanosensing; membrane; stem cells

PMID:
29754801
DOI:
10.1016/j.devcel.2018.04.014
[Indexed for MEDLINE]
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