Identification and Functional Analysis of G Protein-Coupled Receptors in 20-Hydroxyecdysone Signaling From the Helicoverpa armigera Genome

Li, Yanli; Li, Yanxue; Wang, Xiaopei; Kang, Xin-Le; Guo, Ke-Qin; Dong, Du-Juan; Wang, Jinxing; Zhao, Xiao‐Fan

doi:10.3389/fcell.2021.753787

Cited by 5 publications

(5 citation statements)

References 60 publications

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“…In addition, the family of Methuselah genes is known to be involved in longevity and stress resistance [141]. Recent work in Lepidoptera suggests that GPCRs with homology to the Methuselah family of receptors may play important, unresolved roles in mediating the key hormone ecdysone [63], [142]. Importantly, it has been shown that mthl-8 is a potential target of the JNK signaling in the Drosophila eye disc [143].…”

Section: Discussionmentioning

confidence: 99%

The multimodal action of G alpha q in coordinating growth and homeostasis in theDrosophilawing imaginal disc

Velagala

Soundarrajan

Unger

et al. 2023

Preprint

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Background: G proteins mediate cell responses to various ligands and play key roles in organ development. Dysregulation of G-proteins or Ca2+ signaling impacts many human diseases and results in birth defects. However, the downstream effectors of specific G proteins in developmental regulatory networks are still poorly understood. Methods: We employed the Gal4/UAS binary system to inhibit or overexpress Gαq in the wing disc, followed by phenotypic analysis. Immunohistochemistry and next-gen RNA sequencing identified the downstream effectors and the signaling cascades affected by the disruption of Gαq homeostasis. Results: Here, we characterized how the G protein subunit Gαq tunes the size and shape of the wing in the larval and adult stages of development. Downregulation of Gαq in the wing disc reduced wing growth and delayed larval development. Gαq overexpression is sufficient to promote global Ca2+ waves in the wing disc with a concomitant reduction in the Drosophila final wing size and a delay in pupariation. The reduced wing size phenotype is further enhanced when downregulating downstream components of the core Ca2+ signaling toolkit, suggesting that downstream Ca2+ signaling partially ameliorates the reduction in wing size. In contrast, Gαq-mediated pupariation delay is rescued by inhibition of IP3R, a key regulator of Ca2+ signaling. This suggests that Gαq regulates developmental phenotypes through both Ca2+-dependent and Ca2+-independent mechanisms. RNA seq analysis shows that disruption of Gαq homeostasis affects nuclear hormone receptors, JAK/STAT pathway, and immune response genes. Notably, disruption of Gαq homeostasis increases expression levels of Dilp8, a key regulator of growth and pupariation timing. Conclusion: Gαq activity contributes to cell size regulation and wing metamorphosis. Disruption to Gαq homeostasis in the peripheral wing disc organ delays larval development through ecdysone signaling inhibition. Overall, Gαq signaling mediates key modules of organ size regulation and epithelial homeostasis through the dual action of Ca2+-dependent and independent mechanisms.

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Section: Discussionmentioning

confidence: 99%

The multimodal action of G alpha q in coordinating growth and homeostasis in theDrosophilawing imaginal disc

Velagala

Soundarrajan

Unger

et al. 2023

Preprint

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“…Notably, chromosome 1 exhibited the highest density of GPCR genes with nine members. Conversely, chromosomes 12,13,17,19,22,23, and 24 demonstrated relatively low gene density, with no more than two genes present on each. Furthermore, utilizing MCScanX analysis, three instances of tandem duplication events were detected among the octopamine receptor genes, RYamide receptor genes, and Mthls (Figure 1).…”

Section: Identification Of Gpcr Genes In C Pomonellamentioning

confidence: 96%

“…The presence of such genetic diversity, both in terms of genotype and quantity, contributes to the distinct functional characteristics observed across different insect species . For instance, Bombyx mori , Helicoverpa armigera , and Spodoptera frugiperda have been found to possess 93, 122, and 167 GPCRs, respectively. − This variation in the number of genes is proposed to have arisen as an adaptive response to varying environmental pressures. Based on sequence similarity and functional properties, the identified GPCRs in insects are categorized into four families: rhodopsin-like receptors (Class A), secretin receptors (Class B), metabotropic glutamate/pheromone receptors (Class C), and frizzled/smoothened GPCRs (Class F) .…”

Section: Introductionmentioning

confidence: 99%

Identification of G Protein-Coupled Receptors (GPCRs) Associated with Lambda-Cyhalothrin Detoxification in Cydia pomonella

Liu,

Hu,

et al. 2023

J. Agric. Food Chem.

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While previous studies have reported G protein-coupled receptor (GPCR)-mediated insecticide resistance in various arthropods, the understanding of GPCR-associated resistance mechanisms in Cydia pomonella remains limited. In this study, a total of 95 CpGPCR genes categorized into four families were identified in C. pomonella. Results revealed high expression levels of the majority of the CpGPCRs during the first larval stage and in the head of C. pomonella. Exposure to lambda-cyhalothrin significantly increased the expression of 15 CpGPCRs, including CpGPCR70, which is highly expressed in all larval stages and shows the highest expression in the midgut. RNA interference (RNAi) demonstrated that downregulation of CpGPCR70 leads to reduced expression of key resistance-related genes and a decreased tolerance of larvae to lambda-cyhalothrin. These findings indicate that CpGPCR70 plays a crucial role in regulating the expression of detoxifying genes involved in lambda-cyhalothrin resistance, offering valuable insights for the development of more effective pest control strategies.

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“…Wnt signaling starts when the “N‐terminal cysteine‐rich extracellular domain of a Fz family receptor” is bound by a Wnt protein (Chae & Bothwell, 2018). These Fz family receptors span the plasma membranes by sevenfold and constitute a different “G‐protein coupled receptors” (GPCRs) family (Awuchi, 2023; Kramer et al, 2017; Li et al, 2021; Takahashi et al, 2017). Nevertheless, co‐receptors may be required to encourage Wnt signaling along with the interactions between the Fz receptor and the Wnt proteins.…”

Section: Introductionmentioning

confidence: 99%

Wnt/β‐catenin signaling pathway inhibitors, glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, and rutin in medicinal plants have better binding affinities and anticancer properties: Molecular docking and ADMET study

Egbuna

Patrick‐Iwuanyanwu

Onyeike

et al. 2023

Food Science & Nutrition

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Wnt/β‐catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of β‐catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. β‐catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best‐performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, and rutin had the best binding interactions with β‐catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of −8.5 kcal/mol. This was followed by polyphyllin I with −8.4 kcal/mol, and crocin, hypericin, and tubeimoside‐1 which all had a binding energy of 8.1 kcal/mol. Other top‐performing compounds include diosmin and rutin with binding energy of −8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, rutin, and baicalin all violated Lipinski's rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer.

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Identification and Functional Analysis of G Protein-Coupled Receptors in 20-Hydroxyecdysone Signaling From the Helicoverpa armigera Genome

Cited by 5 publications

References 60 publications

The multimodal action of G alpha q in coordinating growth and homeostasis in theDrosophilawing imaginal disc

The multimodal action of G alpha q in coordinating growth and homeostasis in theDrosophilawing imaginal disc

Identification of G Protein-Coupled Receptors (GPCRs) Associated with Lambda-Cyhalothrin Detoxification in Cydia pomonella

Wnt/β‐catenin signaling pathway inhibitors, glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, and rutin in medicinal plants have better binding affinities and anticancer properties: Molecular docking and ADMET study

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