Mutation of the feh-1 gene, the Caenorhabditis elegans orthologue of mammalian Fe65, decreases the expression of two acetylcholinesterase genes.
The molecular adaptor Fe65 is one of the cytosolic ligands of the Alzheimer's beta-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. In Caenorhabditis elegans the 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 the feh-1 gene expression. Here we show that the increased contraction rate of the pharynx in feh-1 mutant worms is associated to decreased acetylcholinesterase activity. The decreased activity is accompanied by reduced expression of ace-1 and ace-2 transcripts, 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.
Bimonte
Marida
M
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini, 5, 80131 Napoli, Italy.
Gianni
Davide
D
Allegra
Danilo
D
Russo
Tommaso
T
Zambrano
Nicola
N
D000110:Acetylcholinesterase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015139:Blotting, Southern / Q000379:methods; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005683:Gagging / Q000187:drug effects; D005786:Gene Expression Regulation / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011715:Pyrantel / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C467198:FEH-1 protein, C elegans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D011715:Pyrantel; D009538:Nicotine; C003407:oxantel; D000110:Acetylcholinesterase