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

doi:10.1002/1873-3468.13579

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^*

^*Kontaktforfatter

Institut for Biokemi og Molekylær Biologi

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Tidsskrift	FEBS Letters
Vol/bind	594
Udgave nummer	1
Sider (fra-til)	31-42
ISSN	1873-3468
DOI	https://doi.org/10.1002/1873-3468.13579
Status	Udgivet - jan. 2020

Finansiering

This work was supported by Austrian Science Fund (FWF), in particular the Lise Meitner Program (FWF) to GL, FWF stand alone P26682_B21to LAH and by the MUI Start Program to CHDS. We acknowledge the Developmental Studies Hybridoma Bank (created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242) as well as K. V. Figura (Georg‐August University of Göttingen) and S. Höning (University of Cologne) for providing antibodies. Thanks are due to K. Gutleben and B. Witting for technical assistance with electron microscopy.

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10.1002/1873-3468.13579Licens: CC BY

Open Access VersionForlagets udgivne version, 2,46 MBLicens: CC BY

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Citationsformater

Lamberti, G., De Smet, C. H., Angelova, M., Kremser, L., Taub, N., Herrmann, C., Hess, M. W., Rainer, J., Tancevski, I., Schweigreiter, R., Kofler, R., Schmiedinger, T., Vietor, I., Trajanoski, Z., Ejsing, C. S., Lindner, H. H., Huber, L. A., & Stasyk, T. (2020). LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation. FEBS Letters, 594(1), 31-42. https://doi.org/10.1002/1873-3468.13579

@article{ee03717e841f402cbd465ac72244b7b6,

title = "LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation",

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 = "foam cells, LAMTOR, macrophages, organelle proteomics, ragulator, transcriptomics",

author = "Giorgia Lamberti and \{De Smet\}, \{Cedric H.\} and Mihaela Angelova and Leopold Kremser and Nicole Taub and Caroline Herrmann and Hess, \{Michael W.\} and Johannes Rainer and Ivan Tancevski and R{\"u}diger Schweigreiter and Reinhard Kofler and Thomas Schmiedinger and Ilja Vietor and Zlatko Trajanoski and Ejsing, \{Christer S.\} and Lindner, \{Herbert H.\} and Huber, \{Lukas A.\} and Taras Stasyk",

year = "2020",

month = jan,

doi = "10.1002/1873-3468.13579",

language = "English",

volume = "594",

pages = "31--42",

journal = "FEBS Letters",

issn = "1873-3468",

publisher = "Wiley",

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Lamberti, G, De Smet, CH, Angelova, M, Kremser, L, Taub, N, Herrmann, C, Hess, MW, Rainer, J, Tancevski, I, Schweigreiter, R, Kofler, R, Schmiedinger, T, Vietor, I, Trajanoski, Z, Ejsing, CS, Lindner, HH, Huber, LA & Stasyk, T 2020, 'LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation', FEBS Letters, bind 594, nr. 1, s. 31-42. https://doi.org/10.1002/1873-3468.13579

TY - JOUR

T1 - LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation

AU - Lamberti, Giorgia

AU - De Smet, Cedric H.

AU - Angelova, Mihaela

AU - Kremser, Leopold

AU - Taub, Nicole

AU - Herrmann, Caroline

AU - Hess, Michael W.

AU - Rainer, Johannes

AU - Tancevski, Ivan

AU - Schweigreiter, Rüdiger

AU - Kofler, Reinhard

AU - Schmiedinger, Thomas

AU - Vietor, Ilja

AU - Trajanoski, Zlatko

AU - Ejsing, Christer S.

AU - Lindner, Herbert H.

AU - Huber, Lukas A.

AU - Stasyk, Taras

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

KW - foam cells

KW - LAMTOR

KW - macrophages

KW - organelle proteomics

KW - ragulator

KW - transcriptomics

U2 - 10.1002/1873-3468.13579

DO - 10.1002/1873-3468.13579

M3 - Journal article

C2 - 31423582

AN - SCOPUS:85071744824

SN - 1873-3468

VL - 594

SP - 31

EP - 42

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

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

Abstract

Finansiering

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Fingeraftryk

Citationsformater