Intestinal apical polarity mediates regulation of TORC1 by glucosylceramide in C. elegans

Abstract

TORC1 (target of rapamycin complex 1) plays a central role in regulating growth, development, and behavior in response to nutrient cues. We previously showed that leucine- derived monomethyl branched-chain fatty acids (mmBCFAs) and derived glucosylceramide promote intestinal TORC1 activity for post-embryonic development and foraging behavior in Caenorhabditis elegans. Here we show that clathrin/adaptor protein 1 (AP-1)-dependent intestinal apical membrane polarity and polarity-dependent localization of the vacuolar-type H+-ATPase (V-ATPase) mediate the impact of the lipid pathway on intestinal TORC1 activation. Moreover, NPRL-3 represses mmBCFA-dependent intestinal TORC1 activity at least partly by regulating apical membrane polarity. Our results provide new insights into TORC1 regulation by lipids and membrane polarity in a specific tissue.