title: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Huanhu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Aileen K
authors.initials: AK
authors.lastname: Sewell
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D005963:Glucosylceramides / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D050356:Lipid Metabolism / Q000502:physiology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D005963:Glucosylceramides; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D025262:Vacuolar Proton-Translocating ATPases
keywords: Nprl2; Nprl3; VHA-6; branched-chain fatty acid; mTOR; sphingolipid