A cadherin‐like protein functions as a receptor for <i>Bacillus thuringiensis</i> Cry1Aa and Cry1Ac toxins on midgut epithelial cells of <i>Bombyx mori</i> larvae

Hara, Hirotaka; Atsumi, Shogo; Yaoi, Katsuro; Nakanishi, Kotoyoshi; Higurashi, Satoshi; Miura, Nami; Tabunoki, Hiroko; Satō, Ryōichi

doi:10.1016/s0014-5793(03)00117-0

Cited by 61 publications

(61 citation statements)

References 48 publications

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“…1B and Movie 1). Cell swelling and lysis occurred within a short time frame (30-40 min after toxin exposure), a phenomenon also observed in other insect cells (9,40) as well as in mammalian cells transfected with the cDNA of BT-R receptors (11). The morphological changes observed in Cry1Ab toxin-treated cells (Fig.…”

Section: Discussionsupporting

confidence: 67%

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A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Zhang

Candas²,

Griko³

et al. 2006

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

365

324

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Many pathogenic organisms and their toxins target host cell receptors, the consequence of which is altered signaling events that lead to aberrant activity or cell death. A significant body of literature describes various molecular and cellular aspects of toxins associated with bacterial invasion, colonization, and host cell disruption. However, there is little information on the molecular and cellular mechanisms associated with the insecticidal action of Bacillus thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin produced by Bt kills insect cells by activating a Mg 2؉ -dependent cytotoxic event upon binding of the toxin to its receptor BT-R1. Here we show that binding of Cry toxin to BT-R1 provokes cell death by activating a previously undescribed signaling pathway involving stimulation of G protein (G␣s) and adenylyl cyclase, increased cAMP levels, and activation of protein kinase A. Induction of the adenylyl cyclase͞protein kinase A pathway is manifested by sequential cytological changes that include membrane blebbing, appearance of ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell death pathway specifically linked to BT-R1 in insect cells should provide insights into how insects evolve resistance to Bt and into the development of new, safer insecticides.Cry toxin ͉ protein kinase A ͉ cadherin receptor ͉ cAMP ͉ signal transduction

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Section: Discussionsupporting

confidence: 67%

“…The specificity of Cry toxins depends on individual cell surface receptors, which represent a family of cadherins expressed in the midgut epithelium of various insects (9)(10)(11)(12)(13). Cytotoxicity and cell death are the direct result of univalent binding of a Cry toxin monomer to its respective cadherin receptor (14).…”

mentioning

confidence: 99%

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Zhang

Candas²,

Griko³

et al. 2006

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

365

324

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“…Nagamatsu et al (129) showed that exposure to 8 g/ml Cry1Aa caused BtR175-expressing Sf9 cells, but not control cells, to swell within 15 min, and the number of swollen cells increased for 45 min after the addition of the toxin. These changes were quite similar to those of midgut columnar cells in B. mori fed with Cry1Aa and to those of epithelial cells isolated from the midgut and treated with toxin ex vivo (66). In another study, Cry1Aa caused cell swelling and cytotoxicity in mammalian cells expressing BtR175b (an allelic variant of BtR175) (171).…”

Section: Btr175 (Bombyx Mori)mentioning

confidence: 59%

“…In contrast, an analysis of the cytoplasmic domain did not reveal sequences known to interact with intracellular proteins such as catenins (33). While classical cadherins are located primarily within adherens junctions involved in cell-cell adhesion (4), lepidopteran cadherin-like proteins have been identified on the apical membrane of midgut columnar epithelial cells (3,24,66,124), the target site of Cry toxins (16,19,20,24). The expression of cadherin has been shown to vary with developmental stage and increases progressively from the first to the fifth instar in M. sexta larvae (124).…”

Section: Cadherinmentioning

confidence: 99%

Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Pigott

Ellar

2007

Microbiol Mol Biol Rev

602

598

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SUMMARY Bacillus thuringiensis produces crystalline protein inclusions with insecticidal or nematocidal properties. These crystal (Cry) proteins determine a particular strain's toxicity profile. Transgenic crops expressing one or more recombinant Cry toxins have become agriculturally important. Individual Cry toxins are usually toxic to only a few species within an order, and receptors on midgut epithelial cells have been shown to be critical determinants of Cry specificity. The best characterized of these receptors have been identified for lepidopterans, and two major receptor classes have emerged: the aminopeptidase N (APN) receptors and the cadherin-like receptors. Currently, 38 different APNs have been reported for 12 different lepidopterans. Each APN belongs to one of five groups that have unique structural features and Cry-binding properties. While 17 different APNs have been reported to bind to Cry toxins, only 2 have been shown to mediate toxin susceptibly in vivo. In contrast, several cadherin-like proteins bind to Cry toxins and confer toxin susceptibility in vitro, and disruption of the cadherin gene has been associated with toxin resistance. Nonetheless, only a small subset of the lepidopteran-specific Cry toxins has been shown to interact with cadherin-like proteins. This review analyzes the interactions between Cry toxins and their receptors, focusing on the identification and validation of receptors, the molecular basis for receptor recognition, the role of the receptor in resistant insects, and proposed models to explain the sequence of events at the cell surface by which receptor binding leads to cell death.

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“…Recently, Gahan et al (2001) discovered a Cry1Ac-resistant Heliothis virescens strain carrying a mutated CadLP gene. Hara et al (2003) demonstrated that an antibody to CadLP (BtR175) inhibits the Cry1A toxin-mediated release of lactate dehydrogenase from midgut cells, thereby supporting the idea that CadLP may be a receptor for Cry1A toxins. Similarly, Gomez et al (2001) reported that a phage display-derived peptide inhibits the specific binding between CadLP and Cry1Ab, whereas it did not disrupt the binding between aminopeptidase N (APN) and Cry1Ab.…”

Section: Introductionmentioning

confidence: 75%

Localization of a novel 252-kDa plasma membrane protein that binds Cry1A toxins in the midgut epithelia of Bombyx mori

Hossain

Shitomi

Nanjo

et al. 2005

Appl. Entomol. Zool.

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We previously demonstrated that a novel 252-kDa protein (P252) isolated from brush border membranes (BBM) of Bombyx mori, hybrid ShureiϫShogetsu, specifically bound Cry1Aa, Cry1Ab and Cry1Ac toxins with a K d of 29, 179 and 20 nM, respectively. P252 was found in a Triton X-100-soluble fraction of BBM from first, third and fifth instar larvae, suggesting that it may be an important element of midgut epithelial cell membranes. P252 was not partitioned into a Triton X-100-insoluble BBM fraction and nearly identical partitioning of P252 was observed using detergents CHAPS and Igepal. These results suggested that P252 localized in non-raft regions of BBM. Immunofluorescence analysis using anti-P252 antiserum demonstrated the existence of P252 in BBMV. Cy3-labeled Cry1Aa, Cry1Ab and Cry1Ac were shown to bind to BBMV, and the addition of anti-P252 antiserum reduced the number of BBMV showing Cy3 fluorescence by 30%. This clearly suggested an important role for P252 in Cry1A binding to BBMV. CD spectra of a mixture of purified P252 with either Cry1Aa, Cry1Ab or Cry1Ac were compared with those of respective free Cry1A toxins and only one of the mixtures (Cry1Aa/P252) was shown to be significantly changed compared to that of native Cry1Aa.

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A cadherin‐like protein functions as a receptor for Bacillus thuringiensis Cry1Aa and Cry1Ac toxins on midgut epithelial cells of Bombyx mori larvae

Cited by 61 publications

References 48 publications

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Localization of a novel 252-kDa plasma membrane protein that binds Cry1A toxins in the midgut epithelia of Bombyx mori

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