Nutritional Control of Stem Cell Division through S-Adenosylmethionine in Drosophila Intestine

Publication date: 26 March 2018
Source:Developmental Cell, Volume 44, Issue 6
Author(s): Fumiaki Obata, Kayoko Tsuda-Sakurai, Takahiro Yamazaki, Ryo Nishio, Kei Nishimura, Masaki Kimura, Masabumi Funakoshi, Masayuki Miura
The intestine has direct contact with nutritional information. The mechanisms by which particular dietary molecules affect intestinal homeostasis are not fully understood. In this study, we identified S-adenosylmethionine (SAM), a universal methyl donor synthesized from dietary methionine, as a critical molecule that regulates stem cell division in Drosophila midgut. Depletion of either dietary methionine or SAM synthesis reduces division rate of intestinal stem cells. Genetic screening for putative SAM-dependent methyltransferases has identified protein synthesis as a regulator of the stem cells, partially through a unique diphthamide modification on eukaryotic elongation factor 2. In contrast, SAM in nutrient-absorptive enterocytes controls the interleukin-6-like protein Unpaired 3, which is required for rapid division of the stem cells after refeeding. Our study sheds light upon a link between diet and intestinal homeostasis and highlights the key metabolite SAM as a mediator of cell-type-specific starvation response.

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Teaser

Obata et al. reveal that S-adenosylmethionine controls intestinal stem cell activity via regulation of protein synthesis. They also demonstrate that this amino acid metabolite mediates the starvation response, fine-tuning gut homeostasis in response to different dietary conditions.


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