title: A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport.
abstract: Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell-autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dowen
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Breen
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tullius
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Conery
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005223:Fats / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2; D035683:MicroRNAs / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction; D040521:Subcutaneous Tissue / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005223:Fats; D035683:MicroRNAs; D046912:Multiprotein Complexes; C583955:PQM-1 protein, C elegans; D015534:Trans-Activators; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: fat metabolism; insulin; mTORC2; microRNAs; pqm-1; vitellogenesis