The microtubule-associated protein tau can accumulate into toxic aggregates seen in multiple neurodegenerative diseases such as Alzheimer's disease and frontotemporal lobar degeneration (FTLD). Mutations in the human gene encoding tau, MAPT, directly cause FTLD. To aid in identifying genetic modulators of human tau-induced toxicity, we used a Caenorhabditis elegans model of tau toxicity. Overexpression of human tau in the neurons of C. elegans causes significant motor dysfunction, progressive loss of neurons, and shortened lifespan. Additionally, these worms accumulate abnormally phosphorylated and detergent insoluble aggregated forms of tau protein. We previously found that loss of both
dop-2 and
dop-3, the D2-like dopamine receptors, significantly ameliorated tau transgene-induced phenotypes. To better understand how loss of D2-like dopamine receptors led to suppression of tau-induced toxicity, we screened mutations in over 40 genes related to dopamine signaling for effects on tau-induced motor dysfunction. We identified
bas-1 as a suppressor of tau-induced motor dysfunction, neuronal loss, and phosphorylated and insoluble tau accumulation. Loss of function in dopamine and/or serotonin synthesis pathway genes such as
cat-2,
tph-1, and
cat-4 did not alter tau-induced toxicity but did reduce
bas-1 suppression of tau-induced toxicity. Additional loss of
dop-2 and
dop-3 did not further improve motor function in tau transgenic C. elegans. This indicates that there is a shared pathway for tau suppression by
bas-1 and the D2-like dopamine receptors, which also requires intact dopamine and serotonin synthesis pathways.