Mutations in the ketothiolase <i>kat-1</i> lead to resistance to exogenous serotonin treatment.

<p>(A) Six mutations in <i>kat-1</i> were identified in a forward genetic screen for resistance to the Nile red accumulation reduction induced by exogenous serotonin. Two mutations (<i>mg449</i> and <i>mg448</i>) led to predicted truncated proteins and therefore the mutations are predicted strong loss of functions. Nucleotide numbers refer to the spliced RNA of <i>kat-1</i> except for <i>mg449</i> where the unspliced <i>kat-1</i> RNA is used as a reference to indicate the loss of a splice donor site. (B) In the absence of exogenous serotonin, <i>kat-1</i> mutants show a more than doubling of LRO Nile red on day 1 of adulthood. (N>25, significance by unpaired, equal variance Student's t-test.) (C) <i>kat-1</i> mutants show attenuated loss of LRO Nile red in response to 55 hours of exogenous serotonin treatment. Wild type worms lose essentially all LRO Nile red, and while <i>kat-1</i> mutants lose approximately the same quantitative amount of LRO Nile red, they preserve 50% of their LRO Nile red level. (N>25, significance by ANOVA with Bonferroni correction.) (D) Wild type and <i>tub-1</i> mutants have full response to serotonin, reducing LRO Nile red to low levels. On the other hand, the <i>kat-1;tub-1</i> double mutant, like the <i>kat-1</i> single mutant, has significant resistance to exogenous serotonin treatment.