Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs.

In mammalian cells, membrane-bound sterol regulatory element-binding proteins (SREBPs) are transported from ER to Golgi where they are processed proteolytically to generate soluble transcription factors that activate lipid synthesis. ER-to-Golgi transport requires SCAP, a sterol-regulated escort protein. In sterol-treated cells, the SCAP/SREBP complex binds to Insig-1 or Insig-2, which retains ...
the complex in the ER, blocking SREBP processing and decreasing lipid synthesis. In Drosophila cells, the endogenous SCAP/SREBP complex is transported to Golgi, but transport is blocked by phosphatidylethanolamine instead of sterols. Here, we show that mammalian SREBP-2 is not transported to Golgi when expressed in Drosophila cells. Transport requires co-expression of mammalian SCAP. Sterols block transport of the mammalian SCAP/SREBP-2 complex, but only when mammalian Insig-1 or -2 is co-expressed. These reconstitution studies define SCAP and Insig as the minimal requirements for sterol-regulated transport of SREBPs from ER to Golgi. They indicate that insect cells can respond to sterols when proper regulatory proteins are expressed.
Mesh Terms:
Animals, Carrier Proteins, Cell Line, DNA-Binding Proteins, Drosophila melanogaster, Endoplasmic Reticulum, Ethanolamine, Genetic Vectors, Golgi Apparatus, Helix-Loop-Helix Motifs, Intracellular Signaling Peptides and Proteins, Mammals, Membrane Proteins, Palmitic Acid, Protein Transport, Proteins, Sterol Regulatory Element Binding Protein 2, Sterols, Transcription Factors
J. Biol. Chem.
Date: Sep. 12, 2003
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