LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation

FEBS Lett. 2020 Jan;594(1):31-42. doi: 10.1002/1873-3468.13579. Epub 2019 Aug 26.

Abstract

Late endosomal/lysosomal adaptor and MAPK and mTOR activator (LAMTOR/Ragulator) is a scaffold protein complex that anchors and regulates multiprotein signaling units on late endosomes/lysosomes. To identify LAMTOR-modulated endolysosomal proteins, primary macrophages were derived from bone marrow of conditional knockout mice carrying a specific deletion of LAMTOR2 in the monocyte/macrophage cell lineage. Affymetrix-based transcriptomic analysis and quantitative iTRAQ-based organelle proteomic analysis of endosomes derived from macrophages were performed. Further analyses showed that LAMTOR could be a novel regulator of foam cell differentiation. The lipid droplet formation phenotype observed in macrophages was additionally confirmed in MEFs, where lipidomic analysis identified cholesterol esters as specifically downregulated in LAMTOR2 knockout cells. The data obtained indicate a function of LAMTOR2 in lipid metabolism.

Keywords: LAMTOR; foam cells; macrophages; organelle proteomics; ragulator; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Cholesterol Esters / metabolism
  • Foam Cells / cytology
  • Foam Cells / metabolism*
  • Lipid Droplets / metabolism
  • Lipid Metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Proteins / genetics
  • Proteins / metabolism*
  • Transcriptome

Substances

  • Cholesterol Esters
  • LAMTOR2 protein, mouse
  • Proteins