Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Huber, MD; Vesely, PW; Datta, K; Gerace, L.
Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis.
J Cell Biol. 2013; 203(3):427-436
Doi: 10.1083/jcb.201305076
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- Co-Autor*innen der Med Uni Graz
- Vesely Paul
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- Abstract:
- Cellular cholesterol levels are controlled by endoplasmic reticulum (ER) sterol sensing proteins, which include Scap and Insig-1. With cholesterol sufficiency, Insig inhibits the activation of sterol regulatory element binding proteins (SREBPs), key transcription factors for cholesterol and fatty acid biosynthetic genes, by associating with Scap-SREBP complexes to promote their ER retention. Here we show that the multimeric ER proteins erlins-1 and -2 are additional SREBP regulators. Depletion of erlins from cells grown with sterol sufficiency led to canonical activation of SREBPs and their target genes. Moreover, SREBPs, Scap, and Insig-1 were physically associated with erlins. Erlins bound cholesterol with specificity and strong cooperativity and responded to ER cholesterol changes with altered diffusional mobility, suggesting that erlins themselves may be regulated by cholesterol. Together, our results define erlins as novel cholesterol-binding proteins that are directly involved in regulating the SREBP machinery. We speculate that erlins promote stability of the SREBP-Scap-Insig complex and may contribute to the highly cooperative control of this system.
- Find related publications in this database (using NLM MeSH Indexing)
- Carrier Proteins - genetics Carrier Proteins - metabolism
- Cell Line, Tumor -
- Cholesterol - metabolism
- Endoplasmic Reticulum - metabolism
- Enzyme Activation -
- HEK293 Cells -
- HeLa Cells -
- Hep G2 Cells -
- Humans -
- Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism
- Lipid Metabolism -
- Membrane Proteins - genetics Membrane Proteins - metabolism
- Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism
- Protein Binding -
- RNA Interference -
- RNA, Small Interfering -
- Sterol Regulatory Element Binding Proteins - metabolism