Catalytic activities of wild‐type C. elegansDAF‐2 kinase and dauer‐associated mutants DOI Open Access
Harini Krishnan, Sultan Ahmed, Stevan R. Hubbard

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 20, 2024

DAF‐2, the Caenorhabditis elegans insulin‐like receptor homolog, regulates larval development, metabolism, stress response, and lifespan. The availability of numerous daf‐2 mutant alleles has made it possible to elucidate genetic mechanisms underlying these physiological processes. DAF‐2 pathway is significantly conserved with human insulin/IGF‐1 signaling pathway; includes proteins homologous IRS, GRB‐2, PI3K, making an important model investigate pathological conditions. We expressed purified kinase domain wild‐type examine catalytic activity substrate specificity enzyme. Like insulin kinase, phosphorylates tyrosines within specific YxN or YxxM motifs, which are for recruiting downstream effectors. phosphorylated peptides derived from motifs located in C‐terminal extension tyrosine consistent idea that may possess independent capacity. Unlike IGF‐1 kinases, was poorly inhibited by small‐molecule inhibitor linsitinib. also kinases corresponding result partial loss‐of‐function phenotypes C. . These mutations caused a complete loss function vitro Our biochemical investigations provide new insights into function, approach should be useful studying other shed light on physiology.

Language: Английский

Activated hedgehog and insulin ligands by decreased transcriptional factor DAF-16 mediate transgenerational nanoplastic toxicity in Caenorhabditis elegans DOI
Jingwei Wu, Yuting Shao,

Xin Hua

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 135909 - 135909

Published: Sept. 19, 2024

Language: Английский

Citations

6
Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior DOI Creative Commons
Jan Watteyne,

Aleksandra Chudinova,

Lidia Ripoll-Sánchez

et al.

Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Neuropeptides are abundant signaling molecules that control neuronal activity and behavior in all animals. Owing part to its well-defined compact nervous system, Caenorhabditis elegans has been one of the primary model organisms used investigate how neuropeptide networks organized these neurochemicals regulate behavior. We here review recent work expanded our understanding neuropeptidergic network C. by mapping evolutionary conservation, molecular expression, receptor–ligand interactions, system-wide organization pathways system. also describe general insights into circuit motifs spatiotemporal range peptidergic transmission have emerged from vivo studies on signaling. With efforts ongoing chart peptide other organisms, connectome can serve as a prototype further understand dynamics at organismal level.

Language: Английский

Citations

5
Esculetin Inhibits Fat Accumulation Through Insulin/Insulin-like Growth Factor- and AMP-Activated Protein Kinase-Dependent Pathways in Caenorhabditis elegans DOI Open Access
Aaron Taehwan Kim, Yeonhwa Park

Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1565 - 1565

Published: May 1, 2025

Background: Esculetin, 6,7-dihydroxycoumarin, is a bioactive compound found in various herbal plants, and known to have health-beneficial properties including anti-obesity effects. However, there lack of vivo studies clearly determine esculetin’s role lipid metabolism. Objectives: In this study, we studied effect on accumulation using Caenorhabditis elegans its underlying mechanisms. Methods: C. were treated with esculetin (100 or 200 μM) for 48 h, their triglyceride protein levels measured. Additionally, behavioral patterns such as pharyngeal pumping rate, body bending sizes, locomotive activity analyzed. Genetic dependencies examined by utilizing mutant worms testing relative gene expressions. Results: displayed significantly reduced fat compared the controls without effects activity. Esculetin’s fat-lowering was dependent DAF-2 (insulin/insulin-like growth factor-1 [IGF-1] receptor homolog), DAF-16 (Forkhead box O AAK-2 (5′-adenosine monophosphate-activated kinase [AMPK] catalytic subunit α2) experiments. Esculetin also increased expression downstream targets (hsp-16.2 sod-3), AMPK-related genes (aak-1 aak-2), sirtuin gene, sir-2.1, lipolysis-related atgl-1. Conclusions: These findings suggest that inhibited insulin/IGF-1 5′-adenosine signaling pathways.

Language: Английский

Citations

0
The signaling landscape of insulin-like growth factor 1 DOI Creative Commons
Muhammad Zahid Khan, José L. Zugaza, Ignácio Torres‐Aleman

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 108047 - 108047

Published: Dec. 1, 2024

Language: Английский

Citations

3
Hormonal regulation and disruption in invertebrates – an historical perspective and recent findings DOI
Anapaula Sommer Vinagre, Angela B. Lange, João C. R. Cardoso

et al.

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 593, P. 112335 - 112335

Published: July 30, 2024

Language: Английский

Citations

0
Catalytic activities of wild‐type C. elegansDAF‐2 kinase and dauer‐associated mutants DOI Open Access
Harini Krishnan, Sultan Ahmed, Stevan R. Hubbard

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 20, 2024

DAF‐2, the Caenorhabditis elegans insulin‐like receptor homolog, regulates larval development, metabolism, stress response, and lifespan. The availability of numerous daf‐2 mutant alleles has made it possible to elucidate genetic mechanisms underlying these physiological processes. DAF‐2 pathway is significantly conserved with human insulin/IGF‐1 signaling pathway; includes proteins homologous IRS, GRB‐2, PI3K, making an important model investigate pathological conditions. We expressed purified kinase domain wild‐type examine catalytic activity substrate specificity enzyme. Like insulin kinase, phosphorylates tyrosines within specific YxN or YxxM motifs, which are for recruiting downstream effectors. phosphorylated peptides derived from motifs located in C‐terminal extension tyrosine consistent idea that may possess independent capacity. Unlike IGF‐1 kinases, was poorly inhibited by small‐molecule inhibitor linsitinib. also kinases corresponding result partial loss‐of‐function phenotypes C. . These mutations caused a complete loss function vitro Our biochemical investigations provide new insights into function, approach should be useful studying other shed light on physiology.

Language: Английский

Citations

0