Sato R et al. (2019), Function and Role of ATP-Binding Cassette Trans...

XB-ART-55719

Toxins (Basel) 2019 Feb 19;112:. doi: 10.3390/toxins11020124.

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Function and Role of ATP-Binding Cassette Transporters as Receptors for 3D-Cry Toxins.

Sato R , Adegawa S , Li X , Tanaka S , Endo H .

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When ABC transporter family C2 (ABCC2) and ABC transporter family B1 (ABCB1) were heterologously expressed in non-susceptible cultured cells, the cells swelled in response to Cry1A and Cry3 toxins, respectively. Consistent with the notion that 3D-Cry toxins form cation-permeable pores, Bombyx mori ABCC2 (BmABCC2) facilitated cation-permeable pore formation by Cry1A when expressed in Xenopus oocytes. Furthermore, BmABCC2 had a high binding affinity (KD) to Cry1Aa of 3.1 × 10-10 M. These findings suggest that ABC transporters, including ABCC2 and ABCB1, are functional receptors for 3D-Cry toxins. In addition, the Cry2 toxins most distant from Cry1A toxins on the phylogenetic tree used ABC transporter A2 as a receptor. These data suggest that 3D-Cry toxins use ABC transporters as receptors. In terms of inducing cell swelling, ABCC2 has greater activity than cadherin-like receptor. The pore opening of ABC transporters was hypothesized to be linked to their receptor function, but this was repudiated by experiments using mutants deficient in export activity. The synergistic relationship between ABCC2 and cadherin-like receptor explains their ability to cause resistance in one species of insect.

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Species referenced: Xenopus
Genes referenced: abcb1 abcc2 cry2 crygdl.43

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References [+] :

Adegawa, The domain II loops of Bacillus thuringiensis Cry1Aa form an overlapping interaction site for two Bombyx mori larvae functional receptors, ABC transporter C2 and cadherin-like receptor. 2017, Pubmed
Aller, Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. 2009, Pubmed
Atsumi, Single amino acid mutation in an ATP-binding cassette transporter gene causes resistance to Bt toxin Cry1Ab in the silkworm, Bombyx mori. 2012, Pubmed
Augustin, Genetics of resistance to transgenic Bacillus thuringiensis poplars in Chrysomela tremulae (Coleoptera: Chrysomelidae). 2004, Pubmed
Banks, Cloning of a Heliothis virescens 110 kDa aminopeptidase N and expression in Drosophila S2 cells. 2003, Pubmed
Baxter, Parallel evolution of Bacillus thuringiensis toxin resistance in lepidoptera. 2011, Pubmed
Bravo, Characterization of cry genes in a Mexican Bacillus thuringiensis strain collection. 1998, Pubmed
Bretschneider, Know your ABCs: Characterization and gene expression dynamics of ABC transporters in the polyphagous herbivore Helicoverpa armigera. 2016, Pubmed
Carroll, Analysis of the large aqueous pores produced by a Bacillus thuringiensis protein insecticide in Manduca sexta midgut-brush-border-membrane vesicles. 1997, Pubmed
Chen, Synergism of Bacillus thuringiensis toxins by a fragment of a toxin-binding cadherin. 2007, Pubmed
Chen, Endogenous expression of a Bt toxin receptor in the Cry1Ac-susceptible insect cell line and its synergistic effect with cadherin on cytotoxicity of activated Cry1Ac. 2015, Pubmed
Chen, Identification and characterization of Aedes aegypti aminopeptidase N as a putative receptor of Bacillus thuringiensis Cry11A toxin. 2009, Pubmed
Crava, Midgut aminopeptidase N isoforms from Ostrinia nubilalis: activity characterization and differential binding to Cry1Ab and Cry1Fa proteins from Bacillus thuringiensis. 2013, Pubmed
Dermauw, The ABC gene family in arthropods: comparative genomics and role in insecticide transport and resistance. 2014, Pubmed
Dorsch, Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to the membrane-proximal extracellular domain of BT-R(1) in Manduca sexta: involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis. 2002, Pubmed
Endo, The intracellular region of silkworm cadherin-like protein is not necessary to mediate the toxicity of Bacillus thuringiensis Cry1Aa and Cry1Ab toxins. 2018, Pubmed
Endo, Water influx via aquaporin directly determines necrotic cell death induced by the Bacillus thuringiensis Cry toxin. 2017, Pubmed
Endo, Cry toxin specificities of insect ABCC transporters closely related to lepidopteran ABCC2 transporters. 2017, Pubmed
Endo, Extracellular loop structures in silkworm ABCC transporters determine their specificities for Bacillus thuringiensis Cry toxins. 2018, Pubmed
Gahan, Identification of a gene associated with Bt resistance in Heliothis virescens. 2001, Pubmed
Gahan, An ABC transporter mutation is correlated with insect resistance to Bacillus thuringiensis Cry1Ac toxin. 2010, Pubmed
Galián, Optimized purification of a heterodimeric ABC transporter in a highly stable form amenable to 2-D crystallization. 2011, Pubmed
Gazit, The structure and organization within the membrane of the helices composing the pore-forming domain of Bacillus thuringiensis delta-endotoxin are consistent with an "umbrella-like" structure of the pore. 1998, Pubmed
Gill, Transgenic Drosophila reveals a functional in vivo receptor for the Bacillus thuringiensis toxin Cry1Ac1. 2002, Pubmed
Guo, The novel ABC transporter ABCH1 is a potential target for RNAi-based insect pest control and resistance management. 2015, Pubmed
Gómez, Cadherin-like receptor binding facilitates proteolytic cleavage of helix alpha-1 in domain I and oligomer pre-pore formation of Bacillus thuringiensis Cry1Ab toxin. 2002, Pubmed
Gómez, Molecular basis for Bacillus thuringiensis Cry1Ab toxin specificity: two structural determinants in the Manduca sexta Bt-R1 receptor interact with loops alpha-8 and 2 in domain II of Cy1Ab toxin. 2003, Pubmed
Hara, A cadherin-like protein functions as a receptor for Bacillus thuringiensis Cry1Aa and Cry1Ac toxins on midgut epithelial cells of Bombyx mori larvae. 2003, Pubmed
Hossain, Characterization of a novel plasma membrane protein, expressed in the midgut epithelia of Bombyx mori, that binds to Cry1A toxins. 2004, Pubmed
Hua, Cadherin AdCad1 in Alphitobius diaperinus larvae is a receptor of Cry3Bb toxin from Bacillus thuringiensis. 2014, Pubmed
Hubbard, SCOP: a structural classification of proteins database. 1997, Pubmed
Jurat-Fuentes, Characterization of a Cry1Ac-receptor alkaline phosphatase in susceptible and resistant Heliothis virescens larvae. 2004, Pubmed
Jurat-Fuentes, The Heliothis virescens cadherin protein expressed in Drosophila S2 cells functions as a receptor for Bacillus thuringiensis Cry1A but not Cry1Fa toxins. 2006, Pubmed
Kitami, Bacillus thuringiensis Cry toxins bound specifically to various proteins via domain III, which had a galactose-binding domain-like fold. 2011, Pubmed
Lemes, Cry1Ac and Vip3Aa proteins from Bacillus thuringiensis targeting Cry toxin resistance in Diatraea flavipennella and Elasmopalpus lignosellus from sugarcane. 2017, Pubmed
Li, Evaluation of the synergistic activities of Bacillus thuringiensis Cry proteins against Helicoverpa armigera (Lepidoptera: Noctuidae). 2014, Pubmed
Liu, A single amino acid polymorphism in ABCC2 loop 1 is responsible for differential toxicity of Bacillus thuringiensis Cry1Ac toxin in different Spodoptera (Noctuidae) species. 2018, Pubmed
Luo, The heliothis virescens 170 kDa aminopeptidase functions as "receptor A" by mediating specific Bacillus thuringiensis Cry1A delta-endotoxin binding and pore formation. 1997, Pubmed
López-Diaz, Oligomerization is a key step in Cyt1Aa membrane insertion and toxicity but not necessary to synergize Cry11Aa toxicity in Aedes aegypti larvae. 2013, Pubmed
Mahon, Resistance to Bacillus thuringiensis toxin Cry2Ab in a strain of Helicoverpa armigera (Lepidoptera: Noctuidae) in Australia. 2007, Pubmed
Martínez, Contents of cry genes and insecticidal toxicity of Bacillus thuringiensis strains from terrestrial and aquatic habitats. 2002, Pubmed
McNall, Identification of novel Bacillus thuringiensis Cry1Ac binding proteins in Manduca sexta midgut through proteomic analysis. 2003, Pubmed
Morin, Three cadherin alleles associated with resistance to Bacillus thuringiensis in pink bollworm. 2003, Pubmed
Nagamatsu, The cadherin-like protein is essential to specificity determination and cytotoxic action of the Bacillus thuringiensis insecticidal CryIAa toxin. 1999, Pubmed
Obata, Induction of rapid and selective cell necrosis in Drosophila using Bacillus thuringiensis Cry toxin and its silkworm receptor. 2015, Pubmed
Ocelotl, ABCC2 is associated with Bacillus thuringiensis Cry1Ac toxin oligomerization and membrane insertion in diamondback moth. 2017, Pubmed
Pandian, Formation of macromolecule complex with Bacillus thuringiensis Cry1A toxins and chlorophyllide binding 252-kDa lipocalin-like protein locating on Bombyx mori midgut membrane. 2010, Pubmed
Pardo-López, Bacillus thuringiensis insecticidal three-domain Cry toxins: mode of action, insect resistance and consequences for crop protection. 2013, Pubmed
Pardo-López, Structural changes of the Cry1Ac oligomeric pre-pore from bacillus thuringiensis induced by N-acetylgalactosamine facilitates toxin membrane insertion. 2006, Pubmed
Paris, Persistence of Bacillus thuringiensis israelensis (Bti) in the environment induces resistance to multiple Bti toxins in mosquitoes. 2011, Pubmed
Park, ABCC transporters mediate insect resistance to multiple Bt toxins revealed by bulk segregant analysis. 2014, Pubmed
Park, Cadherin fragments from Anopheles gambiae synergize Bacillus thuringiensis Cry4Ba's toxicity against Aedes aegypti larvae. 2009, Pubmed
Pauchet, A P-Glycoprotein Is Linked to Resistance to the Bacillus thuringiensis Cry3Aa Toxin in a Leaf Beetle. 2016, Pubmed
Paul, Insecticide resistance in Culex pipiens from New York. 2005, Pubmed
Peña-Cardeña, The C-terminal protoxin region of Bacillus thuringiensis Cry1Ab toxin has a functional role in binding to GPI-anchored receptors in the insect midgut. 2018, Pubmed
Ren, RNA interference-mediated knockdown of three putative aminopeptidases N affects susceptibility of Spodoptera exigua larvae to Bacillus thuringiensis Cry1Ca. 2014, Pubmed
Ridley, Interfacial interactions of pore-forming colicins. 2010, Pubmed
Sangadala, A mixture of Manduca sexta aminopeptidase and phosphatase enhances Bacillus thuringiensis insecticidal CryIA(c) toxin binding and 86Rb(+)-K+ efflux in vitro. 1994, Pubmed
Schwartz, Ion channels formed in planar lipid bilayers by Bacillus thuringiensis toxins in the presence of Manduca sexta midgut receptors. 1997, Pubmed
Soberón, Cell lines as models for the study of Cry toxins from Bacillus thuringiensis. 2018, Pubmed
Stevens, Expressing a moth abcc2 gene in transgenic Drosophila causes susceptibility to Bt Cry1Ac without requiring a cadherin-like protein receptor. 2017, Pubmed
Tabashnik, One gene in diamondback moth confers resistance to four Bacillus thuringiensis toxins. 1997, Pubmed
Tabashnik, Reversal of resistance to Bacillus thuringiensis in Plutella xylostella. 1994, Pubmed
Tabashnik, Cross-resistance of the diamondback moth indicates altered interactions with domain II of Bacillus thuringiensis toxins. 1996, Pubmed
Tanaka, The ATP-binding cassette transporter subfamily C member 2 in Bombyx mori larvae is a functional receptor for Cry toxins from Bacillus thuringiensis. 2013, Pubmed
Tanaka, Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins. 2016, Pubmed
Tanaka, Functional characterization of Bacillus thuringiensis Cry toxin receptors explains resistance in insects. 2016, Pubmed , Xenbase
Tanaka, Response of midgut epithelial cells to Cry1Aa is toxin-dependent and depends on the interplay between toxic action and the host apoptotic response. 2012, Pubmed
Tanaka, Bombyx mori ABC transporter C2 structures responsible for the receptor function of Bacillus thuringiensis Cry1Aa toxin. 2017, Pubmed
Tay, Insect Resistance to Bacillus thuringiensis Toxin Cry2Ab Is Conferred by Mutations in an ABC Transporter Subfamily A Protein. 2015, Pubmed
Tsuda, Cytotoxic activity of Bacillus thuringiensis Cry proteins on mammalian cells transfected with cadherin-like Cry receptor gene of Bombyx mori (silkworm). 2003, Pubmed
Vadlamudi, A specific binding protein from Manduca sexta for the insecticidal toxin of Bacillus thuringiensis subsp. berliner. 1993, Pubmed
Valaitis, Isolation and partial characterization of gypsy moth BTR-270, an anionic brush border membrane glycoconjugate that binds Bacillus thuringiensis Cry1A toxins with high affinity. 2001, Pubmed
Wang, CRISPR/Cas9 mediated genome editing of Helicoverpa armigera with mutations of an ABC transporter gene HaABCA2 confers resistance to Bacillus thuringiensis Cry2A toxins. 2017, Pubmed
Wang, Bacillus thuringiensis Cry1A toxins exert toxicity by multiple pathways in insects. 2018, Pubmed
Wang, Mechanism of resistance to Bacillus thuringiensis toxin Cry1Ac in a greenhouse population of the cabbage looper, Trichoplusia ni. 2007, Pubmed
Xiao, Mis-splicing of the ABCC2 gene linked with Bt toxin resistance in Helicoverpa armigera. 2014, Pubmed
Xie, Genome-wide analysis of the ATP-binding cassette (ABC) transporter gene family in the silkworm, Bombyx mori. 2012, Pubmed
Xie, Single amino acid mutations in the cadherin receptor from Heliothis virescens affect its toxin binding ability to Cry1A toxins. 2005, Pubmed
Xu, Disruption of a cadherin gene associated with resistance to Cry1Ac {delta}-endotoxin of Bacillus thuringiensis in Helicoverpa armigera. 2005, Pubmed
Yaoi, Bacillus thuringiensis Cry1Aa toxin-binding region of Bombyx mori aminopeptidase N. 1999, Pubmed
Zhang, Cytotoxicity of Bacillus thuringiensis Cry1Ab toxin depends on specific binding of the toxin to the cadherin receptor BT-R1 expressed in insect cells. 2005, Pubmed
Zhang, A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis. 2006, Pubmed
Zhao, Different cross-resistance patterns in the diamondback moth (Lepidoptera: Plutellidae) resistant to Bacillus thuringiensis toxin Cry1C. 2001, Pubmed

	Figure 1. Use of ABC transporters as functional receptors by 3D-Cry toxins. Receptor activity data for Cry2Ab using ABC transporter-expressing HEK293T cells or Sf9 cells and previous results for Cry toxins [17,30,31,54]; arrow width indicates the level of activity. Phylogenetic tree of ABC transporters generated using the amino acid sequences of BmABCC2 (BAK82127.1), SeABCC2 (AIB06821.1), BmABCC3 (XP_012547933.1), SeABCC3 (AIB06823.1), TcABCC4 (XP_969849.1), AaABCC4 (APG42670.1), humABCC4 (NP_005836.2), CtABCB1 (APK18402.1), and BmABCA2 (ALE60402.1) with CLUSTAL W. Bm, Bombyx mori; Ct, Chrysomela tremula; Se, Spodoptera exigua; Tc, Tribolium castaneum; Aa, Aedes albopictus. A part of the phylogenetic tree of Cry toxins (Bacillus thuringiensis Toxin Nomenclature; http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/intro.html).
	Figure 2. BmABCC2 structures that affect Cry1As receptor activity. (A) Nucleotide-binding domain-deleted BmABCC2 mutants, D1del and D2del, that exhibit receptor activity for Cry1Aa when expressed in the membranes of Sf9 or HEK293T cells [24]. ECL, extracellular loop. (B) Mutation sites in BmABCC2 that affect receptor activity for Cry1Aa or Cry1Ab [24] and a site at which amino acid replacement increases BmABCC3 receptor activity [54].
	Figure 3. Putative roles of BmABCC2, BmABCC3, and BtR175 in Cry1Aa pore formation. Arrow thickness represents Cry1Aa receptor interaction and pore formation activities [30,31,42,50].