RRC ID 76325
著者 Watterson A, Tatge L, Wajahat N, Arneaud SLB, Solano Fonseca R, Beheshti ST, Metang P, Mihelakis M, Zuurbier KR, Corley CD, Dehghan I, McDonald JG, Douglas PM.
タイトル Intracellular lipid surveillance by small G protein geranylgeranylation.
ジャーナル Nature
Abstract Imbalances in lipid homeostasis can have deleterious effects on health1,2. Yet how cells sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption remains unclear. Here we describe a mechanism for intracellular lipid surveillance in Caenorhabditis elegans that involves transcriptional inactivation of the nuclear hormone receptor NHR-49 through its cytosolic sequestration to endocytic vesicles via geranylgeranyl conjugation to the small G protein RAB-11.1. Defective de novo isoprenoid synthesis caused by lipid depletion limits RAB-11.1 geranylgeranylation, which promotes nuclear translocation of NHR-49 and activation of rab-11.2 transcription to enhance transporter residency at the plasma membrane. Thus, we identify a critical lipid sensed by the cell, its conjugated G protein, and the nuclear receptor whose dynamic interactions enable cells to sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption and lipid metabolism.
巻・号 605(7911)
ページ 736-740
公開日 2022-5-1
DOI 10.1038/s41586-022-04729-7
PII 10.1038/s41586-022-04729-7
PMID 35585236
PMC PMC9885440
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Lipids Monomeric GTP-Binding Proteins* / metabolism Protein Prenylation Receptors, Cytoplasmic and Nuclear / metabolism
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線虫 tm3410