Ma G et al. (2012) Results Immunol "Pre-feeding of a glycolipid binding protein LEC-8 from Caenorhabditis elegans revealed enhanced tolerance to Cry1Ac toxin in Helicoverpa armigera."

Schmidt O, Keller M, Ma G

[Results Immunol, 2012]

Crystal toxins from Bacillus thuringiensis bind to glycolipids and glycoproteins using two different lectin domains in the toxin protein. Our previous observations suggested that the sequestration of crystal toxin depends on the functional interaction of a toxin lectin with glycolipids. Given the finding that competition of a galectin LEC-8 with Cry5B for binding to glycolipids resulting in reduced Bt toxicity in nematode, it is interesting to explore the role of LEC-8 in insects. Here, we reported that the LEC-8 can also be exploited by insect for their survival when they were fed with Bt toxin food. Bioassay with LEC-8 showed that pre-feeding of Helicoverpa armigera larvae reduced the Cry1Ac susceptibility. Both LEC-8 and Cry1Ac bind to the midgut glycolipid in a similar way. Further ELISA indicated that LEC-8 interacts with glycolipid from insect midgut, thus reduce Cry1Ac binding to glycolipid. This in turn enhances insect tolerance to Cry1Ac toxin. The sugar determinants of LEC-8 were studied by using haemagglutination (HA) and haemagglutination inhibition (HAI) assay. It was suggested that the terminal sugar of LEC-8 has multiple sugar binding property.

Ross Francis et al. (2002) East Coast Worm Meeting "APH-1 and PEN-2 are Required for Notch Pathway Signaling, gamma-Secretase Cleavage of betaAPP, and Presenilin Protein Accumulation"

Richard L Myers, Mark Maxwell, Daniel Curtis, Javier Apfeld, Monique Nicoll, Ross Francis, Jinhe Li, Cara Ruble, Jianhuan Zhang, Carol S Himes, Mark Gurney, Garth McGrath, Ronald Hiebsch, Wei Xu, Michael C Ellis, Bing Hai, Annette L Parks, David A Ruddy, Mary Sym, Jeffrey S Nye

[East Coast Worm Meeting, 2002]

Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic enhancer screen revealed two genes, aph-1 and pen-2, encoding conserved multipass transmembrane proteins, that share several properties. Both genes exhibit strong genetic interactions with sel-12/presenilin and aph-2/nicastrin, share the same subset of glp-1/lin-12 pathway phenotypes, and act at or upstream of LIN-12 S3 cleavage. Conserved human APH-1 and PEN-2 proteins are able to partially rescue the C. elegans mutant phenotypes, but only when the two are provided together. Rescue is enhanced when human presenilin 1 is also provided, suggesting that APH-1 and PEN-2 cooperate functionally with one another and with presenilin. Using cultured Drosophila cells, we show that RNAi-mediated inactivation of fly aph-1, pen-2, or nicastrin strongly reduces gamma-secretase cleavage of betaAPP and Notch substrates while also dramatically reducing the accumulation of processed presenilin. These data indicate that APH-1 and PEN-2, like nicastrin, are required for the activity and accumulation of the gamma-secretase complex.