DROSOPHILA-MELANOGASTER ACETYLCHOLINESTERASE - IDENTIFICATION AND EXPRESSION OF 2 MUTATIONS RESPONSIBLE FOR COLD-SENSITIVE AND HEAT-SENSITIVE PHENOTYPES

作者：MUTERO A; BRIDE JM; PRAL**ORIO M; FOURNIER D

来源：Molecular and General Genetics, 1994, 243(6): 699-705.

• ACETYLCHOLINESTERASE
• DROSOPHILA
• THERMOSENSITIVE MUTATION

Ace(IJ29) and Ace(IJ29) are cold- and heat-sensitive variants of the gene coding for acetylcholinesterase in Drosophila melanogaster. In the homozygous condition, these mutations are lethal when animals are raised at restrictive temperatures, i.e., below 23 degrees C for Ace(IJ29) or above 25 degrees C for Ace(IJ40). The coding regions of the gene in these mutants were sequenced and mutations changing Ser(374) to Phe in Ace(IJ29) and pro(75) to Leu in Ace(IJ40) were found. Acetylcholinesterases bearing these mutations were expressed in Xenopus oocytes and we found that these mutations decrease the secretion rate of the protein most probably by affecting its folding. This phenomenon is exacerbated at restrictive temperatures decreasing the amount of secreted acetylcholinesterase below the lethality threshold. In parallel, the substitution of the conserved Asp(248) by an Asn residue completely inhibits the activity of the enzyme and its secretion, preventing the correct folding of the protein in a non-conditional manner.

• 出版日期1994-6-15