Biology subjects

Kashio, S.

Publications and source records attributed to Kashio, S..

4 recordsLinked to original sources

bioRxiv2025

Genome-wide association study shows developmental robustness control by intestinal maltase via internal environment in Drosophila

Organisms encounter disturbances during development because of genetic variations, environmental shifts, and stochastic noise. However, developmental robustness and canalization buffer these fluctuations to maintain normal development. Nevertheless, understanding the underlying mechanisms that govern this robustness is challenging because of the complex interactions between these factors. In Drosophila, the number of scutellar sensory organs (SSO; macrochaetes) derived from the sensory organ precursors (SOPs) in the larval wing disc has been used as a model to study developmental robustness. Although the number of SOPs is strictly regulated by a network of signaling and transcription factors in the imaginal disc, non-intrinsic broader factors such as temperature and energy metabolism additionally influence SSO-number fluctuation. Moreover, the precise molecular mechanisms regulating the systemic control of bristle number remain unknown. In this study, we identify factors controlling bristle robustness by performing genome-wide association studies (GWAS). We observed significant single-nucleotide polymorphisms (SNPs) in the Maltase gene cluster and found that the knockdown of Maltase genes affected SSO numbers. Furthermore, Maltase-A1(Mal-A1) in the gut regulated insulin signaling systemically, thereby affecting SSO-number fluctuation. These results suggest that Mal-A1 contributes to robustness by modulating glucose availability and Drosophila insulin-like peptide 3 (dilp3) level, which affects the SOPs in a nonautonomous manner. This study presents the molecular basis of nutritional regulation of developmental robustness and highlights Maltase as a key mediator.

developmental biology↗

bioRxiv2025

Repressive S-adenosylmethionine biosynthesis status inhibits transcription of HeT-A retrotransposon in the germline of Drosophila.

S-adenosylmethionine (SAM) is the principal cellular donor of methyl moiety in the methylation reaction and regulates gene expression by regulating methylation-related cellular events, such as epigenetic status. Although SAM biosynthesis affects a variety of biological phenomena including disease and aging, whether cell-specific SAM biosynthesis status is present and how it contributes to cellular function are largely unknown. Here, we firstly showed that the Drosophila germline in gametogenesis has a repressive SAM biosynthesis status through the observation of SAM synthetase (Sam-S), a key enzyme for SAM biosynthesis. In addition, our study showed that germline-unique repressive SAM biosynthesis status contributes to inhibition of retrotransposon expression; enhancement of SAM biosynthesis in germline caused excessive expression of retrotransposons including HeT-A, a telomere-specific retroelement, as the most affected target. We found that the promoter activity of HeT-A is enhanced in SAM increased condition with increased accumulation of 6mA DNA methylation, the major DNA methylation modification in the Drosophila genome. Interestingly, the enhanced 6mA enrichment and gene expression in enriched loci were not correlated in other retrotransposons or structural genes. Taken together, our results suggest that SAM-deficient status in the germline uniquely regulates HeT-A transcription via 6mA methylation modification. Thus, our study provides a new understanding of how germline unique metabolic status contributes to regulation of the retrotransposon.

developmental biology↗

bioRxiv2024

Secretome analysis by proximal labeling in Golgi apparatus for identifying fat body derived humoral factors in Drosophila disc regeneration

Humoral factors act as inter-tissue mediators and regulate various organismal physiologies. Although the importance of humoral factors in tissue repair has been recently recognized, our understanding of how humoral proteins regulate tissue repair remains limited. Glycosylation is an important modification of the conventional secretory pathway, and we have demonstrated that N-glycosylation in the Golgi apparatus of the Drosophila fat body (FB), the major secretory tissue equivalent to the mammalian liver and adipose tissue, remotely contributes to epithelial tissue repair. To identify humoral factors that contribute to repair via the Golgi apparatus, we constructed a Golgi-specific protein biotinylation system and performed hemolymph proteomics. By combining genetic analyses, we found that FB-derived innate immune regulators and iron mediators affect tissue repair. Altogether, our Golgi-specific labeling system has the potential to identify Golgi-mediated secreted factors that regulate inter-organ communication.

developmental biology↗

bioRxiv2024

S-adenosylmethionine metabolism buffering is regulated by glycine N-methyltransferase decrease via nuclear ubiquitin-proteasome system

Metabolic homeostasis is essential for survival; however, many studies have focused on the fluctuations of these factors. Furthermore, while metabolic homeostasis depends on the balance between the production and consumption of metabolites, there have been limited investigations into the mechanisms regulating their consumption. S-adenosylmethionine (SAM) metabolism has diverse functions, including methylation, polyamine biosynthesis, and transsulfuration, making its regulation and control crucial. Recent studies have revealed the feedback regulation of SAM production; however, the mechanisms governing its consumption are still poorly understood. In this study, we focused on the stability of SAM levels in the fat body (FB) of Drosophila, which serves as a functional equivalent of the mammalian liver and adipose tissue, under conditions of SAM shortage, including nutrient deprivation. We found that glycine N-methyltransferase (Gnmt), a major SAM-consuming methyltransferase in the FB, decreased via the nuclear ubiquitin-proteasome system (UPS), along with the inhibition of SAM synthesis and starvation. The inhibition of Gnmt degradation by suppression of the nuclear UPS causes starvation tolerance. Thus, the regulation of Gnmt levels through nuclear UPS-mediated degradation helps maintain SAM levels under SAM shortage conditions. Significance StatementS-adenosylmethionine (SAM) metabolism is crucial for diverse functions, which are mediated through methylation process. Although the feedback regulation of SAM production has been explored extensively, our understanding of the mechanism behind SAM consumption remains incomplete. Constant levels of SAM have been observed in Drosophila fat bodies even under conditions of SAM shortage, including nutrient deficiency and inhibition of SAM synthesis. SAM levels are controlled by the degradation of glycine N-methyltransferase (Gnmt), a cytosolic SAM-consuming enzyme, via the nuclear ubiquitin-proteasome system under conditions of SAM shortage. Additionally, the inhibition of Gnmt degradation by suppression of the nuclear UPS causes starvation tolerance. Considering that SAM accumulation promotes energy expenditure in vivo, the starvation-dependent mechanism of Gnmt degradation is important for energy homeostasis.

molecular biology↗