Genomics, GPCRs and new targets for the control of insect pests and vectors

Hill, Catherine A.; Sharan, Shruti; Watts, Val J.

doi:10.1016/j.cois.2018.08.010

Cited by 38 publications

(32 citation statements)

References 48 publications

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“…4C is unknown. However, several previous studies have demonstrated a role for G-protein-coupled receptors (GPCRs) in modulating the expression of P450 genes that lead to resistance (46)(47)(48). These previous findings and the fact that GPCRs can activate the conserved MAPK pathway (49, 50) make these receptors candidate upstream activators of the MAPK-signaling pathway associated with imidacloprid-resistant B. tabaci.…”

Section: Discussionmentioning

confidence: 99%

MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance

Yang

Deng

Wei

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

125

126

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The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by trans-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the trans-regulation of CYP6CM1, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly Bemisia tabaci, by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor cAMP-response element binding protein (CREB). Reporter gene assays were used to identify the putative promoter of CYP6CM1, but no consistent polymorphisms were observed in the promoter of a resistant strain of B. tabaci (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidacloprid-susceptible, IMS). Investigation of potential trans-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor CREB directly regulates CYP6CM1 expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. CREB is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of CREB, and thus the increased expression of CYP6CM1, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.

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Section: Discussionmentioning

confidence: 99%

MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance

Yang

Deng

Wei

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

125

126

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“…However, there are very few insecticides that target GPCRs except the octopamine receptor agonists (Audsley and Down, 2015). Recently, many small molecular chemicals that target insect GPCRs have been proposed for development of new generation insecticides (Sharan and Hill, 2017;Hill et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…However, there are many issues associated with insecticides including evolution of insecticide resistance, threat to beneficial or non-target organisms, and environmental contamination. Therefore, there is an increasing need for discovering and developing new pesticides with novel targets, such as insect GPCRs (Audsley and Down, 2015;Hill et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Physiological functions of a methuselah-like G protein coupled receptor in Lymantria dispar Linnaeus

Cao

Sun

et al. 2019

Pesticide Biochemistry and Physiology

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Insect G protein coupled receptors (GPCRs) have been identified as a highly attractive target for new generation insecticides discovery due to their critical physiological functions. However, few insect GPCRs have been functionally characterized. Here, we cloned the full length of a methuselah-like GPCR gene (Ldmthl1) from the Asian gypsy moth, Lymantria dispar. We then characterized the secondary and tertiary structures of Ldmthl1. We also predicted the global structure of this insect GPCR protein which is composed of three major domains. RNA interference of Ldmthl1 resulted in a reduction of gypsy moths' resistance to deltamethrin and suppressed expression of downstream stress-associated genes, such as P450s, glutathione S transferases, and heat shock proteins. The function of Ldmthl1 was further investigated using transgenic lines of Drosophila melanogaster. Drosophila with overexpression of Ldmthl1 showed significantly longer lifespan than control flies. Taken together, our studies revealed that the physiological functions of Ldmthl1 in L. dispar are associated with longevity and resistance to insecticide stresses. Potentially, Ldmthl1 can be used as a target for new insecticide discovery in order to manage this notorious forest pest.

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“…Primarily because of being such an infamous disease vector for pathogens such as Yellow and Dengue fever, Chikungunya and, as latest addition, Zika arboviruses, all of which summarily are responsible for affecting approximately 50-100 million people per year, with the majority of these attributed to Dengue virus infection (Baud et al, 2017; Price et al, 2015; Saiz et al, 2016). Secondly, knowledge on the interaction of the ligands with their respective receptor are thought to be very helpful for drug research using specific GPCRs as targets for development of selective biorational insecticides (Audsley and Down, 2015; Hill et al, 2018; Verlinden et al, 2014). Another reason was that each of the three neuropeptide systems has already been partially investigated, thus, this study could build on previous research data.…”

Section: Introductionmentioning

confidence: 99%

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

Wahedi

GÄde

Paluzzi

2019

Preprint

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Genomics, GPCRs and new targets for the control of insect pests and vectors

Cited by 38 publications

References 48 publications

MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance

MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance

Physiological functions of a methuselah-like G protein coupled receptor in Lymantria dispar Linnaeus

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

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