Biology subjects

Ringuet, M.

Publications and source records attributed to Ringuet, M..

3 recordsLinked to original sources

bioRxiv2024

Food entrainment in mice leads to sex- and organ-specific responses in nutrient metabolism

Food intake is one of the main zeitgebers in the digestive system; however, little is known about organ- and sex-specific differences in food-driven regulation. We placed male and female C57Bl/6 mice on time-restricted feeding (TRF), limiting the food intake period to 8 hours. Food was added either at dark (ZT12) or light (ZT0) onset for 14 days. Afterwards, an additional 4-hour delay in the feeding period was introduced for half of the mice, and the TRF regime continued for another 14 days. TRF from ZT12 to ZT20 led to the highest weight gain in females but the lowest in males while improving intestinal transepithelial resistance (TEER) in both sexes. However, it also led to the disappearance of food-anticipatory response in several hepatic genes. Delaying the start of TRF until ZT16 led to an increase in weight gain and a decrease in fasting plasma glucose levels in male mice, as well as to strong entrainment of metabolism-related hepatic and duodenal genes in both sexes. The alignment of food intake with the early lights-on phase (ZT0-ZT8) caused only minor changes in physiological responses. However, it did lead to an overall downregulation of hepatic and an upregulation of duodenal and gastric genes, with additional loss of food-anticipatory gene expression in both sexes. Delaying the start of food intake until ZT4 was highly detrimental, causing an increase in fasting blood glucose levels, a decrease in TEER, and further disruptions in gene expression patterns in the stomach and liver. In contrast, the duodenum was able to restore its food-driven gene expression. These results demonstrate that the adjustment to food intake time in mice is highly sex- and organ-specific. Our chosen TRF regimes were not able to synchronize food-anticipatory responses between the liver and gut. Instead, we observed that organs entrain to food intake at different rates.

molecular biology↗

bioRxiv2023

Re-coding of G protein-coupled receptor signaling enables emergent cellular behavior.

All cells face the challenge of integrating multiple extracellular signals to produce relevant physiological responses. Different combinations of G protein-coupled receptors, when co-expressed, can lead to distinct cellular outputs, yet the molecular basis for this co-operativity is controversial. One such interaction is the reversal, from inhibition to excitation, at the dopamine D2 receptor in the ghrelin receptors presence, relevant for defecation control. Here we demonstrate that this reversal of dopamine D2 activity, to excitatory, occurs through a dominant switch in downstream signaling. This dominant switch, mediated by downstream signaling, enables fidelity in cellular responses not possible under alternative models, and provides an explanation for previously unresolved observations. Importantly, the switch in D2 signaling does not require ghrelin receptor agonism, rather its constitutive activity, thus accounting for the importance of central nervous system-ghrelin receptor in the absence of endogenous ligands. This re-coding has important implications for our understanding of how atypical receptor pharmacology can occur as well as how sequential signaling at individual neurons may be encoded to produce new outputs.

cell biology↗

bioRxiv2022

Ubiquitination of the GluA1 subunit of AMPA receptors is required for synaptic plasticity, memory and cognitive flexibility

Activity-dependent changes in the number of AMPA-type glutamate receptors (AMPARs) at the synapse underpin the expression of long-term potentiation (LTP) and long-term depression (LTD), cellular correlates of learning and memory. Post-translational ubiquitination has emerged as a key regulator of the trafficking and surface expression of AMPARs, with ubiquitination of the GluA1 subunit at Lys-868 controlling the post-endocytic sorting of the receptors into the late endosome for degradation, and thereby regulating their stability at synapses. However, the physiological significance of GluA1 ubiquitination remains unknown. In this study, we generated mice with a knock-in mutation in the major GluA1 ubiquitination site (K868R) to investigate the role of GluA1 ubiquitination in synaptic plasticity, learning and memory. Our results reveal that these mice have normal basal synaptic transmission but exhibit enhanced LTP and deficits in LTD. They also display deficits in short-term spatial memory and cognitive flexibility. These findings underscore the critical roles of GluA1 ubiquitination for bidirectional synaptic plasticity and cognition.

neuroscience↗