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 abcb6 abcc2 cry2 crygdl.43

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	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].