Biology subjects

Robciuc, M.

Publications and source records attributed to Robciuc, M..

3 recordsLinked to original sources

bioRxiv2026

Nutrient-responsive midgut turnover is spatially controlled by serotonin signaling

Barrier epithelia undergo rapid turnover, yet how spatial tissue heterogeneity and environmental cues shape turnover rates remains poorly understood. Here, we show that serotonin signaling spatially regulates homeostatic turnover of the Drosophila midgut epithelium in a nutrient-responsive manner. Organ-wide analysis revealed regions of constitutively high and low turnover, as well as areas whose renewal depends on nutrient intake. In rapidly renewing posterior regions, serotonin accumulates in enterocytes undergoing programmed cell death (erebosis) in response to nutrient availability. Serotonin signals through the conserved 5HT7 receptor to promote enteroblast (EB) maturation and migration-associated morphological changes. 5HT7 signaling is both necessary and sufficient for renewal in high-turnover regions, and its sustained disruption leads to epithelial multilayering. Mechanistically, 5HT7 signaling regulates genes involved in metabolic pathways, such as the serine biosynthesis pathway, and in the actin cytoskeleton, which drive EB maturation and morphological change, respectively. Together, our findings establish a signaling mechanism that links nutritional cues to the spatial regulation of barrier epithelium turnover.

physiology↗

bioRxiv2026

Evolutionary conservation and divergence of regional fructose-responsive gene regulation in the intestine

Sugar-responsive gene regulation in peripheral organs facilitates safe utilization of fructose. Intestine is the first-line site for fructose catabolism, converting fructose into less harmful metabolites. Its metabolism is spatially organized along the proximodistal axis, but how intestinal zonation shapes responses to fructose and to what extent these responses are evolutionarily conserved remain poorly understood. Here, we examine regional gene regulation in response to acute fructose challenge across the small intestine of mouse and Drosophila. Fructose exposure elicited both ubiquitous and regionally biased regulation of metabolic genes. Unlike prolonged feeding on a complex high-carbohydrate diet, fructose feeding activated the heat shock and immune responses, with proximal and distal biases, respectively. The ChREBP/Mondo-Mlx pathway emerged as the major regulator of fructose-responsive gene expression, with a conserved role in regulation of both ubiquitous and region-restricted metabolic targets. Comparative analysis of orthologous genes revealed conserved activation of glucose metabolism, nutrient transport, and stress-responsive pathways, but also notable divergence in downstream metabolic programs. Whereas mouse intestine activates pathways required for fructose conversion into glucose, Drosophila preferentially activates de novo lipogenesis. Thus, intestinal gene regulation provides a conserved protective mechanism against high fructose challenge, but the pathways involved have partially diverged during evolution.

genomics↗

bioRxiv2024

MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism

The heterodimeric ChREBP-MLX transcription factor complex is a key mediator that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called Carbohydrate Responsive Element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated, remains poorly understood. Here we show that MLX phosphorylation on an evolutionarily conserved motif is necessary for the heterotetramer formation on the ChoRE and the transcriptional activity of the ChREBP-MLX complex. We identified CK2 and GSK3 as MLX kinases that coordinately phosphorylate MLX. High intracellular glucose-6-phosphate accumulation inhibits MLX phosphorylation and heterotetramer formation on the ChoRE, impairing ChREBP-MLX activity. Physiologically, MLX phosphorylation is necessary in Drosophila to maintain sugar tolerance and lipid homeostasis. Our findings suggest that MLX phosphorylation is a key mechanism for the ChREBP-MLX heterotetramer formation to regulate carbohydrate and lipid metabolism.

cell biology↗