Abstract
The ATP-binding cassette (ABC) transporter gene family is ubiquitous in the living world. ABC proteins bind and hydrolyze ATP to transport a myriad of molecules across various lipid-containing membrane systems. They have been studied well in plants for transport of a variety of compounds and particularly, in vertebrates due to their direct involvement in resistance mechanisms against several toxic molecules/metabolites. ABC transporters in insects are found within large multigene families involved in the efflux of chemical insecticides and toxic/undesired metabolites originating from food and endogenous metabolism. This review deals with ABC transporter subfamilies of few agronomically important Lepidopteran pests. The transcriptional dynamics and regulation of ABC transporters during insect development emphasizes their functional diversity against insecticides, Cry toxins, and plant specialized metabolites. To generate insights about molecular function and physiological roles of ABCs, functional and structural characterization is necessary. Also, expansion and divergence of ABC transporter gene subfamilies in Lepidopteran insects needs more systematic investigation. We anticipate that newer methods of insect control in agriculture can benefit from an understanding of ABC transporter interactions with a vast range of natural specialized molecules and synthetic compounds.
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Introduction
Annually, around 590,000 tons of insecticides are used worldwide for safe-guarding crops in the field and during storage (Sharma et al. 2019). It is well known that some of the target insect species have developed resistance against insecticides such as organophosphates, dichlorodiphenyltrichloroethane, pyrethroids, and carbamates (reviewed by Dawkar et al. 2013). The phenomenon of resistance in insects is due to their diverse and efficient adaptive mechanisms. These mechanisms include detoxification, target site modifications, and nerve insensitivity (McCaffery et al. 1997). Detoxification of specific molecules is one of the mechanisms to adapt to resistance. It involves reduction of substrate toxicity by cytochrome P450 monooxygenases (Scott and Wen 2001; Wu et al. 2021), conversion of hydrophobic toxic compounds to hydrophilic products by glutathione-S-transferases, uridine diphosphate glucuronosyl transferases and carboxyl esterases (Pan et al. 2019; Hilliou et al. 2021; Meng et al. 2022), and efflux of conjugated xenobiotics from the cell mainly by the ATP-binding cassette (ABC) transporters (Dawkar et al. 2013; Hilliou et al. 2021).
ABC transporters are widespread across all species and represent one of the most prominent transmembrane protein families (Hull et al. 2014). ABC transporters comprise an intracellular domain to bind and hydrolyze ATP to transport molecules like inorganic ions, sugars, amino acids, lipids, peptides, specialized metabolites, and xenobiotic agents across membranes (Higgins 1992). These transporters are divided into three categories based on their functions: (i) importers—found exclusively in prokaryotes, transport mainly ions, sugars, amino acids, peptides, and other hydrophilic molecules, (ii) exporters—present in prokaryotes and eukaryotes, involved in the transport of hydrophobic compounds like lipids, fatty acids, drugs, endogenous and exogenous toxins, and (iii) non-transport proteins—act as ion channels or their regulators and receptors, function in the mechanism of DNA repair, participate in the assembly of ribosomes and in protein translation (Beek et al. 2014). A functional ABC transporter comprises two domains: Nucleotide-Binding Domain (NBD) and Transmembrane Domain (TMD) (Higgins 1992). Further, the ABC transporter superfamily is classified into eight subfamilies (ABCA to H), based on NBD sequence similarity and the arrangement of NBD and TMD (Dean et al. 2001; Dermauw and Van Leeuwen 2014).
Insect ABC transporters are also required for several physiological and metabolic processs such as (i) molting and cuticle tissue differentiation (Broehan et al. 2013), (ii) egg development and germ cell migration (Ricardo and Lehman 2009; Broehan et al. 2013), (iii) transport of eye pigment molecules, and (iv) biochemical processes like uric acid uptake (Wang et al. 2013). An overview of Lepidopteran ABC transporters and their varied functions has been provided in Table 1. While insect ABC transporters, in general, have been discussed earlier, this review aims to focus especially on the order, Lepidoptera.
Lepidopteran larvae damage economically important plants and their parts, causing heavy agronomical losses especially at the pre-harvest level. For example, the cotton bollworm (Helicoverpa armigera Hubn., Lepidoptera: Noctuidae) is a devastating pest of several important crops such as chickpea (Cicer arietinum L.), cotton (Gossypium species), tomato (Solanum lycopersicum) feeding on pods, bolls, and fruits, respectively. Further, H. armigera is known to infest over 300 different plants, including important food and cash crops (Kotkar et al. 2009). The diamondback moth (Plutella xylostella L., Lepidoptera: Plutellidae), a specialist insect of Brassicaceae members, is a severe threat to the worldwide production of cauliflower and cabbage. Its short life cycle and development of resistance against almost all known insecticides poses a challenge to control its infestation. Other members of Lepidoptera include silk moth (Bombyx mori L.), Asian cotton leafworm (Spodoptera litura F.), tobacco hawkmoth (Manduca sexta L.), navel orangeworm moth (Amyelois transitella W), Asiatic rice borer moth (Chilo suppressalis W.), fall armyworm (Spodoptera frugiperda S.), cabbage looper (Trichoplusia ni Hubn.), cotton pink bollworm (Pectinophora gossypiella S.), and small white butterfly (Pieris rapae L.). In this review, detoxification mechanisms employed by Lepidopteran insects using ABC transporters have been discussed emphasizing their sequence and structural complexity, evolutionary attributes, and their key functions.
Structural Facets of Lepidopteran ABC Proteins
Lepidopteran ABC proteins exhibit structural features similar to other eukaryotic ABC transporters. ABC transporters couple movement of substrate(s) across the membrane by hydrolysis of a phosphate bond between α and β-phosphate of ATP (Higgins 1992). Two TMDs with multiple membrane-spanning α-helices together form specific binding site(s) and a pathway that transports substrate(s) across a lipid bilayer. They couple conformational changes induced by ATP binding, its hydrolysis, and ADP release. A full transporter consists of two TMDs and two NBDs. These domains are structurally similar and generate an internal twofold (or pseudo twofold) symmetry to form a functional unit (Higgins and Linton 2004). As mentioned previously, eukaryotic ABC transporters are exporters. Few of these belong to the Multidrug-Resistant Protein (MRP) class that mediate resistance to xenobiotics (Labbé et al. 2011). On the contrary, prokaryotic importers are selective for a single or a few related water-soluble substrates. Eukaryotic exporters either have a single polypeptide chain containing all the domains or a dimer of two polypeptides, each having one NBD and one TMD as found in bacterial exporters (Beek et al. 2014). NBD is responsible for the hydrolysis of ATP needed to provide energy for transport. Also, NBDs share a common evolutionary origin as they are structurally similar (Linton 2007). They are a subgroup of the diverse superfamily of P-loop NTPase (Vetter and Wittinghofer 2001) and require Mg2+ ions for catalysis. Each NBD has a core of 200 amino acids and two sub domains, the RecA-like domain and a more diverse α-helical domain unique to ABC proteins (Beek et al. 2014). Conserved motif analysis for Lepidopteran ABC proteins was carried out using MEME server (Fig. 1; Supplementary File 1). NBDs are identified based on a signature loop (LSGGQ; Fig. 1A) and seven conserved motifs, A-loop, P-loop, Walker A (Fig. 1B), Walker B, D-loop, H-loop, and a Q-loop (Fig. 1C). The Walker A motif is a phosphate-binding loop with highly conserved lysine residues. Amide nitrogen and ε group of lysine residues form interactions with β- and γ-phosphate of ATP. The Walker B motif identified by ϕϕϕϕDE (where ϕ is a hydrophobic amino acid) coordinates with Mg2+ via an aspartate residue. Glutamate acts as a general base, polarizing the attack of the water molecule. LSGGQ is located at the N-terminus of the α-helical subdomain that directs positive charge of the helical dipole toward γ-phosphate of ATP (Beek et al. 2014). The Walker B motif is followed by the D-loop (SALD motif). Alteration in the confirmation of D-loop affects conformation of the catalytic site and formation of ATP hydrolysis site. The A-loop contains a conserved aromatic residue, usually a tyrosine that helps to position ATP via stacking with the adenine ring. The Q-loop is eight residues long and is identified by the presence of glutamine. It is located at the interface between the RecA-like and the α-helical subdomain. This site of NBDs undergoes interaction with the TMDs. The Q-loop undergoes conformational changes allowing the conserved glutamine residue to move in and out of the active site during the hydrolysis cycle. The site is activated when Mg-ATP is bound (Beek et al. 2014).
TMDs are α-helices embedded in membranes (Dermauw and Van Leeuwen 2014; Locher 2016). They can show diversity in the number of alpha-helices and are therefore highly variable. NBDs are coupled to different TMDs. Such coupling creates a vast number of combinations generating diversity of ABC proteins (Higgins and Linton 2004). Lepidopteran ABC proteins show a topology similar to other eukaryotes, possessing either half or full transporters (Xiong et al. 2015). They can be single (either NBD or TMD), ABC2 (NBD-NBD), half (TMD-NBD or NBD-TMD) or full (TMD-NBD-TMD-NBD or NBD-TMD-NBD-TMD) transporters (Fig. 1D). TMDs from ABC proteins are classified into nine categories according to the Pfam database, out of which four have been reported in eukaryotes (Xiong et al. 2015). TMDs reported in Lepidoptera are as follows: ABC2_membrane TMDs (PF01061) in ABCA subfamily, ABC_membrane TMDs (PF00664) in ABCB and ABCC subfamily, ABC_membrane_2 TMDs (PF06472) (Supplementary Table 1) in ABCD subfamily, and ABC2_membrane_3 (PF12698) in ABCG subfamily. ABCA proteins exhibit TMD-NBD-TMD-NBD and is a full transporter (Dermauw and Van Leeuwen 2014; Liu 2011; Xiong et al. 2015; Tian et al. 2017). Some ABC transporters encode half structures and need to dimerize to form fully functional transporters (Dermauw and Van Leeuwen 2014). The subfamilies ABCA-C domain structures showed the presence of TMD-NBD-TMD-NBD full transporters (Sturm et al. 2009; Dermauw and Van Leeuwen 2014). Our analyses depict that Lepidopteran ABC transporters have structural diversity across their subfamilies. ABCE protein contains four highly conserved motifs present selectively in this subfamily. In the Pfam database, PF00005 class of NBD is present across all subfamilies (Supplementary Table 1). ABCE and ABCF transporters do not have TMDs, but their NBDs are linked, suggesting an atypical characteristic. ABCG subfamily members are half transporters, also showing reverse orientation (NBD-TMD) with NBD at the N-terminal of TMD and dimerize to a functional transporter. ABCH proteins show inverse half-transporter architecture similar to the ABCG proteins. This immense structural variability within ABC sub-families leads further to their divergence and expansion.
Divergence and Lineage-Specific Expansion of Lepidopteran ABC Transporters
We have constructed a phylogenetic tree using 72 ABC protein sequences from 11 candidate Lepidopteran insects retrieved from the National Centre for Biotechnology Information (NCBI) (Fig. 2; Supplementary File 1). The criterion for selecting these insects was based on their importance in agriculture and as model systems. As expected, the phylogenetic analysis depicts that Lepidopteran ABC proteins form distinct 8 clades corresponding to ABCA to H subfamilies. The evolution of eukaryotic ABCs, in general, has been studied using a sequence analysis of NBDs and TMDs separately. We have presented a phylogeny based on the full-length sequences of representative Lepidopteran ABC proteins. As observed in eukaryotes, ABCB, ABCC, and ABCD classify into one group, while ABCB and ABCC cluster together. ABCE and ABCF subfamilies that do not possess TMDs group together and are involved in functions other than transport (Xiong et al. 2015). ABCA and ABCG group together in eukaryotic NBD- and TMD-based tree, but we find a dissimilar trend in our analysis. We noticed that ABCA and ABCH subfamilies cluster together to form a clade; similarly, ABCB and ABCC form a different clade (Fig. 2). This depicts that in Lepidopteran ABC transporters, ABCA and ABCH are closely related. As observed in other eukaryotes, gene duplication events are dominant in ABCC and ABCG clades, implicating expansion in the number of genes in these subfamilies compared to other ABC subfamilies (Sturm et al. 2009; Labbé et al. 2011). Interestingly, Lepidopteran P-glycoprotein (P-gp) expansion is not species-specific, suggesting gene expansion across all its members (Denecke et al. 2021). Specifically, ABCC and ABCG families involved in insecticide resistance have diversified TMDs adapting to the transport of different substrates (Dermauw and Van Leeuwen 2014).
Differential Expression of ABC Transporters Indicates Their Role in Efflux of Plant Specialized Metabolites
The selection of host plants by insects is dependent on nutritional and ecological features. This eventually directs adaptation to particular plants or plant families, grouping insects as monophagous, oligophagous, and polyphagous, or broadly, generalist and specialist feeders. However, during feeding on different food, polyphagous Lepidopteran larvae face several challenges. Various proteinaceous plant defensive molecules and non-proteinaceous plant specialized metabolites are encountered throughout the larval (feeding) stages. Such specialized plant defensive molecules include phenolics, quinones, flavonoids, tannins, terpenoids, proanthocyanidins, lignins, glucosinolates, amino acids, proteins (digestive enzyme inhibitors, lectins, defensins), malondialdehyde, and herbivore-induced plant volatiles (HIPVs) (War et al. 2012).
Intense selection pressure by these deleterious dietary compounds might have led to the rapid evolution of transport mechanisms in insects, such as the development of specific detoxification pumps (Labbé et al. 2011). In herbivores, gut efflux transporters as counter-mechanisms to plant specialized metabolites have been reported (Sorenson and Dearing 2006). An important example is the blood–brain barrier (BBB) in M. sexta, a specialist feeder of Nicotiana spp. A BBB is a protective epithelium that excludes nicotine from the sensitive neuropile using detoxifying enzymes and a nicotine pump. This nicotine pump is an ABCB1 transporter homolog that excretes plant metabolites like nicotine, vinblastine, morphine, and atropine (Maddrell and Gardiner 1975; Murray et al. 1994; Gaertner and Morris 1999). Further, P-gp has also been reported to be involved in the efflux of non-polar cardenolides. For example, access of digoxin to the nerve cord is prevented by an active efflux carrier (Petschenka et al. 2013).
Further, when insects are fed on different plant metabolites, expression of ABC transporters during various stages of their life cycle and in different tissues varies considerably. For example, when H. armigera larvae were reared on an artificial diet supplemented with host (atropine-scopolamine, nicotine, and tomatine) and non-host (taxol) plant metabolites, the highest number of differentially expressed ABC transporter genes was found in the gut as compared to the other tissues (Bretschneider et al. 2016). However, these results indicated that several ABC transporters were upregulated, while compound-specific expression pattern was not apparent. Conversely, members of subfamilies B and C reported for xenobiotic detoxification were upregulated in M. sexta gut upon feeding on different Solanaceous plants and a non-host, rapeseed (Brassica napus), highlighting the importance of ABC transporters in larval plasticity and adaptability on host plants (Koenig et al. 2015). Preferential expression of ABC transporters in P. xylostella Malpighian tubules and midgut predicted their involvement in detoxifying specialized plant metabolites (Qi et al. 2016). In vivo and in vitro evidence of HaABCB6 in the metabolism of gossypol in H. armigera has been presented (Jin et al. 2020). In a nutshell, toxic metabolites and their intermediates travel through various metabolic pathways, potentially mediated by ABC transporters, to be either used for a physiological function or then, to be excreted (Fig. 3). Thus, studies on ABC transporters will provide a platform for interrogating whether they show specificity for a particular class of plant specialized metabolites, mainly in polyphagous insects that survive in a complex ecological niche, for example, comprising even host plant-associated microbiota.
ABC Transporter Gene Expression in Insects and Their Correlation with Insecticide Resistance
P-gp is a permeability glycoprotein also known as MDR1; multi-drug resistance protein 1 or ABCB1 (Srinivas et al. 2004). It has been found that insecticides such as monocrotophos, endosulfan, cypermethrin, fenvalerate, and methyl parathion stimulate ATPase activity of P-gp in H. armigera (Aurade et al. 2006). Susceptibility of H. armigera larvae to indoxacarb, tebufenozide, chlorpyrifos, lambda-cyhalothrin, and abamectin upon treatment with a P-gp inhibitor, verapamil, has been reported (Jin et al. 2019). Expression of other subfamilies such as ABCC and ABCG increased in response to several insecticides like pirimicarb, thiodicarb, abamectin, avermectin, emamectin benzoate, ivermectin, and thiamethoxam (Dermauw and Van Leeuwen 2014). In the red flour beetle (Tribolium castaneum), silencing of two TcABCC genes by RNAi resulted in an increase in susceptibility to malathion. On the contrary, there was no significant increase in insecticide-induced mortalities upon knocking down TcABC genes in the larvae treated with cyfluthrin and diacylhydrazine tebufenozide (TBF insecticides) (Rosner and Merzendorfer 2021).
Consider an example of P. xylostella, the first reported insect to develop resistance against DDT in 1950s and later to Bacillus thuringiensis toxins in 1990s (Ankersmit 1953; Shelton et al. 1993). ABC transporters are upregulated more frequently in insecticide-resistant strains of P. xylostella than the expression of GSTs, COEs or P450s (You et al. 2013). Also, ABCA, ABCC, ABCF, ABCG, and ABCH subfamily members were over-expressed in chlorpyrifos-resistant strain of P. xylostella (Qi et al. 2016). Nevertheless, such observations cannot be extrapolated to other Lepidopteran members. Further, synergism studies in C. suppressalis larvae showed that treatment with verapamil, a potent inhibitor of ABCs, resulted in significantly increased toxicity of chlorantraniliprole involving upregulation of CsABCC8, CsABCG1C, and CsABCH1 (Meng et al. 2020). However, upregulation of genes alone is insufficient to demonstrate resistance, demanding an insight into its mechanism (Denecke et al. 2017; Figuera-Mansur et al. 2013). So further functional studies are needed to confirm involvement of upregulated candidate ABCs in insecticide resistance. The development of new molecules for the control of agricultural pests demands a thorough investigation into their binding efficiency with ABC transporters to avoid the pitfall of resistance.
ABCs Play Key Role in Bt Resistance Strategies Employed by Insects
A recent review by Heckel (2021) summarizes advancements in the role of ABC transporters in Bt resistance of Lepidoptera. Cry toxins from Bacillus thuringiensis (Bt) toxin form pores in the larval midgut epithelium to eventually lyse the cells. These toxins are known as PFTs (pore-forming toxins), produced during the sporulation phase of growth. The sequential binding model for Cry toxin proposes binding to cadherin and further to receptor proteins (aminopeptidase N; APN and alkaline phosphatase; ALP) in the membrane. Membrane pores are formed leading to osmotic stress and cell death (Gomez et al. 2014; Andrés-Garrido et al. 2020). Cry1 toxins are effective against polyphagous noctuid and non-noctuid pests. However, P. xylostella, T. ni, Plodia interpunctella, P. gossypiella, and H. armigera have long been reported for resistance against Bt toxin (Alvi et al. 2012; Fabrick et al. 2015; Janmaat and Myers 2003; Lei et al. 2014; McGaughey 1985; Tabashnik et al. 1994). Bt resistance in Lepidoptera comprises mutations in toxin receptors such as aminopeptidase N (APN), cadherin, alkaline phosphatase (ALP), and ABC transporters (Knight et al. 1994; Vadlamudi et al. 1995; Jurat-Fuentes and Adang 2004; Gahan et al. 2010; Tanaka et al. 2016).
Several ABC subfamilies are linked with Bt resistance. ABCC1 acts as a functional receptor to Cry2Ab toxin (Chen et al. 2018), while the ABCC2 helps Cry1Ac in oligomerization and membrane insertion (Ocelotl et al. 2017). CRISPR/Cas9 single and double knockouts of HaABCC2 and HaABCC3 have demonstrated resistance against Cry1Ac and Cry1Fa (Wang et al. 2020; Zhao et al. 2021). Similarly, a single amino acid change in ABCC2 loop 1 is responsible for difference in toxicity of Cry1Ac in S. frugiperda and S. litura (Liu et al. 2018). Enhanced metabolic resistance to chemical insecticides in P. xylostella has been speculated to increased ABCC2 expression (Xu et al. 2020). Not only ABCC and ABCG subfamilies, but also the ABCA2 subfamily corroborates with Cry1A and Cry2A resistance in H. armigera and H. punctigera (Tay et al. 2015). This has been further confirmed by reports on mutations in ABCA2 that confer resistance to Cry2Ab in T. ni and P. gossypiella (Mathew et al. 2018; Yang et al. 2019; Fabrick et al. 2021). Cry1Fa and Cry1A.105 resistance are due to loss-of-function mutations in the ABCC2 gene in S. frugiperda (Flagel et al. 2018; Boaventura et al. 2020; Banerjee et al. 2017). Also, regulation of resistance to Cry1Ac in Lepidoptera has been attributed to a conserved target site of microRNA-998–3p, identified from the coding sequence of ABCC2 (Zhu et al. 2020). Many conclusions are drawn from laboratory experiments. However, it is essential to examine insects from the field to analyze naturally occurring mutations that impart resistance. Conclusively, it is interesting to note that down regulation of ABCG (Pxwhite) from P. xylostella is linked to Cry1Ac resistance (Guo et al. 2015a). Whereas, in yet another example, PxABCH is an essential gene with a mechanism independent of Cry1Ac resistance independent of Cry1Ac resistance suggesting its significance as a potential target for pest control (Guo et al. 2015b; Zuber et al. 2018). Genetically engineered crops harboring Bt insecticidal proteins have been demonstrated to be a boon in agriculture and are therefore cultivated worldwide. Investigations into ABC-Cry protein interactions provide a strong platform for the development of future genetically engineered crops.
Lepidopteran ABC Transporters Demonstrate Functional Diversity
Several reports indicate functional diversity of ABC transporters in Lepidoptera. To understand the physiological functions of ABC transporters, gene expression-based studies, RNA interference (RNAi), and CRISPR/Cas9 have been widely used.
Apart from their role in detoxification, functional analysis of ABC transporters in H. armigera using CRISPR/Cas9-induced mutations established their role in pigment transport to the cytoplasm (Khan et al. 2017). The role of ABC transporters in development is evident in the case of silkworm, where homolog of the white gene, Bmwh3, a member of ABCG subfamily, transports ommochrome precursors and uric acid into pigment and urate granules, respectively. The white, brown, and scarlet proteins transport guanine or tryptophan in Drosophila melanogaster Meigen. (Fruit fly) (Diptera: Drosophilidae) (Ewart et al. 1994; Komoto et al. 2009). Other subfamilies such as ABCE and ABCF are not considered as transporters, due to the absence of the TMD (Dean et al. 2001; Bretschneider et al. 2016). Their function in transcription, translation, and ribosome assembly has been reported (Tyzack et al. 2000). In yet another interesting study, larval and pupal mortality was demonstrated in P. xylostella by suppressing the expression of PxABCH1 using RNAi (Guo et al. 2015b). Thus, the involvement of Lepidopteran ABC transporters ranging from the transport of molecules required in several important physiological processes and in the detoxification of xenobiotics implies their functional diversity.
Conclusion and Future Perspectives
Insect ABCs are essential for detoxifying xenobiotics and the transport of substances involved in critical physiological processes. In particular, ABC transporters from Lepidopteran insect pests exposed to various chemicals are involved in the efflux of plant metabolites, chemical insecticides, and Bt toxins. Available literature on insect ABC transporters reveals diversification and evolution for various substrates transported by them. The expression profiles of candidate ABC transporter genes during different stages of insect development explain their functional diversity. For example, in insects, ABC transporters have a role in transport of pigment molecules responsible for eye color. As a future perspective, based on the vast knowledge resource available on this topic, we suggest following studies on ABC transporters:
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1.
ABC transporter-plant specialized metabolite interaction using in silico analysis and further validation by experiments to unravel binding specificity.
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2.
Elucidating three-dimensional crystal structures of insect ABC transporters with and without ligands (binding partners).
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3.
Deciphering the rationale for the presence of large number of ABC transporter subfamily members in general, and in particular, in Lepidopteran insects.
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4.
Evaluate their roles in transport of different substrates.
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5.
Provide functional evidence(s) to support development of resistance against new chemicals used for control of insects as well as metabolites from host and non-host plants.
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6.
Interaction of ABC transporters with Bt toxin for the formation of a membrane pore.
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7.
Demonstrate sequential metabolism (if any) of xenobiotics and whether it is general or specific.
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8.
Exploring the potential of ABCH for the control of agricultural insect pests.
Since ABC transporters are important especially in agricultural insects, it is necessary to understand their function to design counter-strategies for minimizing crop losses and enhancing productivity.
Abbreviations
- ABC:
-
ATP-binding cassette
- NBD:
-
Nucleotide-binding domain
- TMD:
-
Transmembrane domain
- AChE:
-
Acetylcholinesterase
- APN:
-
Aminopeptidase N
- ALP:
-
Alkaline phosphatase
- HIPV:
-
Herbivore-induced plant volatiles
- Bt:
-
Bacillus thuringiensis
- MDR:
-
Multidrug-resistance
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Acknowledgements
HMK is grateful to the Department of Science and Technology- Science and Engineering Board (DST-SERB; EEQ/2017/000691), Government of India for funding. PRB thanks Council of Scientific and Industrial Research (CSIR), New Delhi for the award of Junior and Senior Research Fellowship. MBT thanks Department of Science and Technology, New Delhi for the award of Women Scientist Fellowship. APG and RSJ acknowledge project funding from the CSIR under Agriculture, Nutrition and Biotechnology theme (MLP101526), and seed grant (MLP036626) to CSIR-National Chemical Laboratory. We are grateful to Dr. Prashant Mendki for his critical reading. We are extremely thankful to the anonymous reviewer for useful suggestions to improve our manuscript.
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Barve, P.R., Tellis, M.B., Barvkar, V.T. et al. Functional Diversity of the Lepidopteran ATP-Binding Cassette Transporters. J Mol Evol 90, 258–270 (2022). https://doi.org/10.1007/s00239-022-10056-2
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DOI: https://doi.org/10.1007/s00239-022-10056-2