Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

Mikdache, Aya; Boueid, Marie-José; Spek, Lorijn van der; Lesport, Emilie; Delespierre, Brigitte; Loisel‐Duwattez, Julien; Degerny, Cindy; Tawk, Marcel

doi:10.1038/s41598-021-92758-z

Cited by 6 publications

(1 citation statement)

References 62 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, this study lays the foundation for elucidating the molecular mechanism of environmental regulation of nutrient metabolism in S. constricta. MHY1485 is an activator of mTOR in human cancer cells, osteoblast cells [23], chicken granulosa cells [24], porcine macrophages [25], mouse hepatocytes [26], and Danio rerio [27]. Rapamycin has been studied as an inhibitor of mTOR in human cancer cells [28], Mus musculus [29], Danio rerio [30], Drosophila [31], Xenopus laevis [32], Saccharomyces cerevisiae [33], and Brachionus calyciflorus [34].…”

Section: Introductionmentioning

confidence: 99%

mTOR Plays a Conserved Role in Regulation of Nutritional Metabolism in Bivalve Sinonovacula constricta

Zhou

Li²,

Liao

et al. 2023

JMSE

View full text Add to dashboard Cite

The mammalian target of rapamycin (mTOR) has been shown to play a central role in regulating cell growth and metabolism. However, little is known about the function of mTOR in nutrient metabolism in bivalve mollusks. In this study, the role of mTOR in the regulation of nutrient metabolism was investigated in Sinonovacula constricta. First, the activation of mTOR was assayed after starvation and refeeding. Afterwards, the role of mTOR in the regulation of nutrient metabolism was investigated using an activator (MHY1485) or inhibitor (rapamycin) of mTOR. The open reading frame of the S. constricta mTOR is 7416 bp in length and encodes a polypeptide consisting of 2471 amino acids. The mTOR amino acid sequence of S. constricta was highly conserved when compared with other species and had a close evolutionary relationship with the TOR proteins of Crassostrea gigas and Lingula anatine. mTOR was expressed in the intestine, exhalent siphon, labial palppus, muscle, inhalent siphon, gill, mantle, digestive land, and gonad tissue of S.constricta, with the highest expression in muscle. During starvation, the level of phosphorylated mTOR protein was relatively low, and the ratio of LC3II/LC3I protein and the AMPKα mRNA level significantly increased with the increase in starvation time. After feeding, the level of phosphorylated mTOR protein increased from 0.13 to 0.56, and the ratio of LC3II/I protein and AMPKα mRNA level decreased from 1.17 to 0.38. MHY1485 significantly increased the level of phosphorylated 4E-BP1 and significantly decreased the ratio of LC3II/I proteins. Furthermore, MHY1485 significantly increased the mRNA level of the glucose metabolism-related gene glucokinase (GK), significantly decreased the mRNA expression of the G6P gene, and significantly increased the mRNA expression of the lipid synthesis-related genes sterol-regulatory element-binding protein (SREBP) and stearoyl-CoA desaturase (SCD). Rapamycin significantly reduced the level of phosphorylated 4E-BP1 and the mRNA expression of mTOR, and the expression level of phosphorylated 4EBP1 decreased from 0.97 to 0.28. Meanwhile, it also significantly reduced the mRNA expression of glucose metabolism-related genes GK, pyruvate kinase (PK), glucose transporter 1 (GLUT1), and G6P, as well as lipid synthesis-related genes SCD and acetyl-CoA carboxylase (ACC). These results indicate a conserved role of mTOR in regulating nutritional metabolism, including glucose metabolism, lipid synthesis, and autophagy in S. constricta.

show abstract

Section: Introductionmentioning

confidence: 99%

mTOR Plays a Conserved Role in Regulation of Nutritional Metabolism in Bivalve Sinonovacula constricta

Zhou

Li²,

Liao

et al. 2023

JMSE

View full text Add to dashboard Cite

show abstract

Nano-alumina induced developmental and neurobehavioral toxicity in the early life stage of zebrafish, associated with mTOR

Zhang,

He,

Wang

et al. 2024

Aquatic Toxicology

View full text Add to dashboard Cite

Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids

Capauto,

Wang,

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~ 7000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~ 35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community.

show abstract

Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

Cited by 6 publications

References 62 publications

mTOR Plays a Conserved Role in Regulation of Nutritional Metabolism in Bivalve Sinonovacula constricta

mTOR Plays a Conserved Role in Regulation of Nutritional Metabolism in Bivalve Sinonovacula constricta

Nano-alumina induced developmental and neurobehavioral toxicity in the early life stage of zebrafish, associated with mTOR

Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids

Contact Info

Product

Resources

About