Mutation of thefeh-1gene, theCaenorhabditis elegansorthologue of mammalian Fe65, decreases the expression of two acetylcholinesterase genes.

The molecular adaptor Fe65 is one of the cytosolic ligands of the Alzheimer'sβ-amyloid precursor protein (APP), and this complex is believed to play important roles in mammalian cells. Upon cleavage of APP by specific processing activities, the complex between Fe65 and the APP intracellular domain (AICD) translocates to the nucleus. Experimental evidence suggests that the Fe65-AICD complex regulates gene transcription. InCaenorhabditis elegansthe orthologue of the Fe65 gene,feh-1, regulates pharyngeal activity. In fact, the rate of pharyngeal contraction is increased following transient or stable suppression of thefeh-1gene expression. Here we show that the increased contraction rate of the pharynx infeh-1mutant worms is associated to decreased acetylcholinesterase activity. The decreased activity is accompanied by reduced expression oface-1andace-2transcripts, coding for the two major acetylcholinesterase activities in the nematode. These results indicate a target of the regulatory mechanisms based on the Fe65-APP complex that could be relevant for the pathogenesis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]