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

Giorgia Lamberti, Cedric H. De Smet, Mihaela Angelova, Leopold Kremser, Nicole Taub, Caroline Herrmann, Michael W. Hess, Johannes Rainer, Ivan Tancevski, Rüdiger Schweigreiter, Reinhard Kofler, Thomas Schmiedinger, Ilja Vietor, Zlatko Trajanoski, Christer S. Ejsing, Herbert H. Lindner, Lukas A. Huber, Taras Stasyk*

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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.

OriginalsprogEngelsk
TidsskriftFEBS Letters
Vol/bind594
Udgave nummer1
Sider (fra-til)31-42
ISSN1873-3468
DOI
StatusUdgivet - jan. 2020

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