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LPS‐induced mTORC1 Signaling Activates Lipid Raft‐Actin Cytoskeletal Interactions for Phagocytosis through SREBP‐1a
Author(s) -
Lee JaeHo,
Kim Do Young,
Lee Sun Hee,
Song DaeKyu,
Bae JaeHoon,
Im SeungSoon
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb318
Subject(s) - microbiology and biotechnology , lipid raft , mtorc1 , sterol regulatory element binding protein , phagocytosis , biology , actin cytoskeleton , lipid metabolism , innate immune system , macrophage , cytoskeleton , signal transduction , immune system , biochemistry , pi3k/akt/mtor pathway , cell , sterol , immunology , cholesterol , in vitro
There is a growing appreciation for a fundamental connection between lipid metabolism and the immune response. Macrophage phagocytosis is a signature innate immune response to pathogen exposure and cytoplasmic membrane expansion is required to engulf the phagocytic target. The sterol regulatory element binding proteins (SREBPs) are key transcriptional regulatory proteins that sense the intracellular lipid environment and modulate expression of key genes of fatty acid and cholesterol metabolism to maintain lipid homeostasis. In this study, we show that TLR4 dependent stimulation of macrophage phagocytosis requires mTORC1‐directed SREBP‐1a dependent lipid synthesis. We also show that the phagocytic defect in macrophages from SREBP‐1a deficient mice results from decreased interaction between membrane lipid rafts and the actin cytoskeleton presumably due to reduced accumulation of newly synthesized fatty acyl chains within major membrane phospholipids. We show that mTORC1 deficient macrophages also have a phagocytosis block downstream from TLR4 signaling, and interestingly, the phagocytosis deficiency in both SREBP‐1a and mTORC1 mutant macrophages can be restored by ectopic SREBP‐1a expression. Taken together, these observations indicate SREBP‐1a is a major downstream effector of TLR4‐mTORC1 directed interactions between membrane lipid rafts and the actin cytoskeleton that are required for pathogen‐stimulated phagocytosis in macrophages. Support or Funding Information The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP)(2016R1A2B4008516). The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2014R1A5A2010008). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .