A multifunctional protein, calreticulin, in pathway(s) of volatile anesthetics in Drosophila

Drosophila mutants with altered sensitivity to diethyl ether have been used to elucidate the action mechanisms of volatile anesthetics. One of them, ethas311, was a mutation in calreticulin gene (crc) and showed resistance to isoflurane and hypersensitivity to diethyl ether. These phenotypes were associated with low expression of mRNA of the gene. In this study, the endogenous calreticulin proteins were analyzed by Western blots and immunohistochemistry. It revealed that calreticulin distributed on the same regions of the mRNA expressed indicating the proteins functioned in the same cells, and the relative amount of the protein decreased in the adult brain of the mutant. To speculate how to act diethyl ether on calreticulin, some other crc mutants, which defect aversive odor avoidance, were assayed for diethyl ether EC50s. They were homolethal but their heterozygotes were fertile and showed hypersensitivity to diethyl ether. These results suggested that calreticulin plays important role(s) in the volatile anesthetic pathway(s), which relates to olfactory system. I discussed pathway(s) of diethyl ether anesthesia that calreticulin could be mediated by regulation of cell adhesion and/or cell movement, and loss of short-term memory in olfactory memory system.