Multiple Receptors as Targets of Cry Toxins in Mosquitoes

Abstract

Bacillus thuringiensis (Bt) produce inclusions that are composed of proteins known as crystal proteins or Cry toxins. Due to their high specificity and their safety to humans and the environment these Cry toxins are considered valuable alternatives to chemical pesticides in insect control programs. It is believed that Cry toxin-induced membrane pore formation is responsible for insect toxicity. The molecular mechanism of pore formation involves recognition and subsequent binding of the toxin to membrane receptors. This binding is accompanied by toxin oligomerization and transfer of domain I helices of the toxin to the lipid-water interface. This toxin insertion creates pores that lyse the cells. Several receptors from lepidopteran, coleopteran, and dipteran insects have been well characterized. Here we provide an overview of our understanding of the interactions between Cry toxin and multiple receptors in mosquitoes, in particular Aedes aegypti. We review the manner by which the receptors were identified and characterized, with a focus on three proteins – cadherin, alkaline phosphatase and aminopeptidase-N.

A Spodoptera exigua Cadherin Serves as a Putative Receptor for Bacillus thuringiensis Cry1Ca Toxin and Shows Differential Enhancement of Cry1Ca and Cry1Ac Toxicity

“…Similarly, cadherins in seven lepidopteran, two dipteran, and two coleopteran species have been confirmed or suggested to be receptors for other Cry toxins (2,(12)(13)(14)(15)(16).…”

“…Until now, insect cadherins have been proven or suggested to interact with Cry toxins in at least six lepidopteran (2), two dipteran (12)(13)(14), and two coleopteran (15,16) species. A toxin-binding cadherin receptor is composed of five domains: signal peptide (SP), 8 to 12 cadherin repeats (CRs), membrane-proximal extracellular domain (MPED), transmembrane region (TM), and internal cytoplasmic domain (IC) (17).…”

Current models of the mode of action of Bacillus thuringiensis insecticidal crystal proteins: A critical review

“…It describes a hypothetical mechanism of pore formation which is largely based on work dealing with Cry1Ab and Manduca sexta. Like the closely related toxins Cry1Aa and Cry1Ac, Cry1Ab is recognized, in several lepidopteran insect species such as M. sexta, by at least two specific receptors in the luminal membrane of midgut epithelial cells: a cadherin-like protein and a glycosyl-phosphatidylinositol (GPI)-anchored aminopeptidase N (Gómez et al, 2007;Likitvivatanavong et al, 2011;Pigott and Ellar, 2007). According to the initial version of the sequential binding model, once activated by intestinal proteases, the toxin binds to the cadherin.…”

“…In fact, a vast literature describes the involvement of several membrane-bound proteins, including aminopeptidase N and, more recently, alkaline phosphatase, as well as glycolipids (Griffitts et al, 2005), in toxin binding and pore formation (Gómez et al, 2007;Likitvivatanavong et al, 2011;Pigott and Ellar, 2007).…”

“…For instance, the structure of the pores formed by the toxins and the mechanism by which they assemble into the membrane have not been fully elucidated. On the other hand, considerable progress has been accomplished in the identification of Cry toxin receptors and understanding of their role in toxin recognition as well as in resistance to these toxins (see Gómez et al (2007), Likitvivatanavong et al (2011) and Pigott and Ellar (2007) for detailed reviews). Otherwise, research on the mode of action of Cry toxins has been dominated in recent years by two models, the sequential binding model (Fig.…”