Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes

Axel Nohturfft, Daisuke Yabe, Joseph L. Goldstein, Michael S. Brown, Peter Espenshade

Research output: Contribution to journalArticle

Abstract

SREBPs exit the ER in a complex with SCAP. Together, they move to the Golgi where SREBP is cleaved, releasing a fragment that activates genes encoding lipid biosynthetic enzymes. Sterols block ER exit, preventing cleavage, decreasing transcription, and achieving feedback control of lipid synthesis. Here, we report an in vitro system to measure incorporation of SCAP into ER vesicles. When membranes were isolated from sterol-depleted cells, SCAP entered vesicles in a reaction requiring nucleoside triphosphates and cytosol. SCAP budding was diminished in membranes from sterol-treated cells. Kinetics of induction of budding in vitro matched kinetics of ER exit in living cells expressing GFP-SCAP. These data localize the sterol-regulated step to budding of SCAP from ER and provide a system for biochemical dissection.

Original languageEnglish (US)
Pages (from-to)315-323
Number of pages9
JournalCell
Volume102
Issue number3
StatePublished - Aug 4 2000
Externally publishedYes

Fingerprint

Sterols
Cholesterol
Membranes
Feedback
Cells
Lipids
Dissection
Kinetics
Gene encoding
Transcription
Nucleosides
Cytosol
Feedback control
Enzymes
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nohturfft, A., Yabe, D., Goldstein, J. L., Brown, M. S., & Espenshade, P. (2000). Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell, 102(3), 315-323.

Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. / Nohturfft, Axel; Yabe, Daisuke; Goldstein, Joseph L.; Brown, Michael S.; Espenshade, Peter.

In: Cell, Vol. 102, No. 3, 04.08.2000, p. 315-323.

Research output: Contribution to journalArticle

Nohturfft, A, Yabe, D, Goldstein, JL, Brown, MS & Espenshade, P 2000, 'Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes', Cell, vol. 102, no. 3, pp. 315-323.
Nohturfft A, Yabe D, Goldstein JL, Brown MS, Espenshade P. Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell. 2000 Aug 4;102(3):315-323.
Nohturfft, Axel ; Yabe, Daisuke ; Goldstein, Joseph L. ; Brown, Michael S. ; Espenshade, Peter. / Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. In: Cell. 2000 ; Vol. 102, No. 3. pp. 315-323.
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