Involvement 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.