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Coordination of lipid synthesis during membrane biogenesis
Author(s) -
Nohturfft Axel,
Castoreno Adam B.,
Wang Yan,
Bojkovic Jade,
Stockinger Walter,
Jarzylo Larissa A.,
Du Hong,
Shieh Eugenie C.,
Pag Joanne C.
Publication year - 2006
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.20.4.a520-d
Subject(s) - sterol regulatory element binding protein , phagocytosis , biogenesis , microbiology and biotechnology , biochemistry , lipid droplet , fatty acid synthesis , chemistry , sterol , cholesterol , biology , fatty acid , gene
In the process of membrane biogenesis several dozen proteins must operate in precise concert to generate about 100 lipids at appropriate concentrations. To study the regulation of bilayer assembly in a cell cycle‐independent manner we have exploited the fact that phagocytes replenish membranes expended during particle engulfment in a rapid phase of lipid synthesis. In response to phagocytosis of latex beads, cultured human phagocytes synthesized cholesterol and phospholipids at amounts equivalent to the surface area of the internalized particles. Phagocytosis triggered the proteolytic activation of two lipogenic transcription factors, sterol regulatory element binding protein‐1a (SREBP‐1a) and SREBP‐2. Upon inhibition of SREBPs, phagocytosis‐induced transcription of lipogenic proteins and lipid synthesis were blocked, identifying SREBPs as central regulators of membrane biogenesis. In addition to this central mode of control, membrane lipid synthesis is coordinated ‘horizontally’: following phagocytosis, addition of cholesterol synthesis inhibitors blocked synthesis of both cholesterol and phospholipids. Conversely, inhibition of fatty acid synthesis prevented the synthesis of phospholipids as well as cholesterol. The mechanisms of cross‐regulation are being investigated.