biostudies-literatureIke YPromotion of Science (JSPS) Grant-in-Aid for Scientific Researchiyac025https://www.ebi.ac.uk/biostudies/studies/S-EPMC8982016biostudies-literatureUnknown220(4)The ubiquitin-proteasome system is associated with various phenomena including learning and memory. In this study, we report that E3 ubiquitin ligase homologs and proteasome function are involved in taste avoidance learning, a type of associative learning between starvation and salt concentrations, in Caenorhabditis elegans. Pharmacological inhibition of proteasome function using bortezomib causes severe defects in taste avoidance learning. Among 9 HECT-type ubiquitin ligase genes, loss-of-function mutations of 6 ubiquitin ligase genes cause significant abnormalities in taste avoidance learning. Double mutations of those genes cause lethality or enhanced defects in taste avoidance learning, suggesting that the HECT-type ubiquitin ligases act in multiple pathways in the processes of learning. Furthermore, mutations of the ubiquitin ligase genes cause additive effects on taste avoidance learning defects of the insulin-like signaling mutants. Our findings unveil the consequences of aberrant functions of the proteasome and ubiquitin systems in learning behavior of Caenorhabditis elegans.GeneticsInvolvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans.PMC8982016JP17H06113Tomioka MIino YIke YfalseInvolvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans.The ubiquitin-proteasome system is associated with various phenomena including learning and memory. In this study, we report that E3 ubiquitin ligase homologs and proteasome function are involved in taste avoidance learning, a type of associative learning between starvation and salt concentrations, in Caenorhabditis elegans. Pharmacological inhibition of proteasome function using bortezomib causes severe defects in taste avoidance learning. Among 9 HECT-type ubiquitin ligase genes, loss-of-function mutations of 6 ubiquitin ligase genes cause significant abnormalities in taste avoidance learning. Double mutations of those genes cause lethality or enhanced defects in taste avoidance learning, suggesting that the HECT-type ubiquitin ligases act in multiple pathways in the processes of learning. Furthermore, mutations of the ubiquitin ligase genes cause additive effects on taste avoidance learning defects of the insulin-like signaling mutants. Our findings unveil the consequences of aberrant functions of the proteasome and ubiquitin systems in learning behavior of Caenorhabditis elegans.2022-01-01T00:00:00Z2022 Apr2025-04-20T03:03:06.39Z2025-04-20T03:03:06.39ZS-EPMC89820163517614710.1093/genetics/iyac025