Inhibition of proteolysis, and presumably activation of a protease target, appears to be required for proper formation of long-term memory in Drosophila. Comas et al. used a genetic screen to isolate a Drosophila mutant that has a deficit in long-term memory in response to a training protocol. The affected gene encodes a protein, Cer, that closely resembles the N-terminal portion of some members of the cathepsin family of cysteine proteinases. Usually this N-terminal portion inhibits cathepsin activity of the catalytic portion of the same molecule, but Cer seems to be a separate inhibitory molecule. In fact, protein-protein interaction maps indicate that Cer interacts with three cathepsin-like proteins from the fly, two of which lack the usual inhibitory N-terminal region. Formation of long-term memory seemed to require just the right amount of Cer. The Cer protein is expressed in neuronal and glial cells, and too much Cer, as a result of overexpression of Cer in glial cells, also caused a decrease in long-term memory. In wild-type flies, amounts of Cer mRNA and protein were transiently reduced 3 hours after training. These studies and others (see Related Resources) suggest new dimensions to the roles of cathepsins in signaling.
D. Comas, F. Petit, T. Preat, Drosophila long-term memory formation involves regulation of cathepsin activity. Nature 430, 460-463 (2004). [Online Journal]
