We have used a genetic screen for mutations that result in defects in the development of AFT to identify two transcriptional co-repressors, ctbp-1 and pag-3, that regulate the ability of animals to develop AFT. Transcriptional repression of the lips-7 TAG lipase is required for normal development of AFT, and loss of lips-7 enhances the rate and degree of AFT, indicating that action of this lipase inhibits the development of AFT. One component of the normal development of AFT appears to involve modulation of the ethanol effect on the transmembrane ethanol target protein SLO-1, and the function of SLO-1 gain-of-function mutations is modulated by the action of lips-7, suggesting that there is a role for TAGs in the regulation of SLO-1 function. Depletion of cholesterol impaired the development of AFT and, while cholesterol is used both as a component of the plasma membrane and as a precursor to steroid synthesis in the worm, taken together, these data suggest a role for membrane microdomain structure in AFT.
