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Lipase maturation factor 1 affects redox homeostasis in the endoplasmic reticulum
- Publication Year :
- 2018
- Publisher :
- John Wiley and Sons Inc., 2018.
-
Abstract
- Lipoprotein lipase (LPL) is a secreted lipase that clears triglycerides from the blood. Proper LPL folding and exit from the endoplasmic reticulum (ER) require lipase maturation factor 1 (LMF1), an ER‐resident transmembrane protein, but the mechanism involved is unknown. We used proteomics to identify LMF1‐binding partners necessary for LPL secretion in HEK293 cells and found these to include oxidoreductases and lectin chaperones, suggesting that LMF1 facilitates the formation of LPL's five disulfide bonds. In accordance with this role, we found that LPL aggregates in LMF1‐deficient cells due to the formation of incorrect intermolecular disulfide bonds. Cells lacking LMF1 were hypersensitive to depletion of glutathione, but not DTT treatment, suggesting that LMF1 helps reduce the ER. Accordingly, we found that loss of LMF1 results in a more oxidized ER. Our data show that LMF1 has a broader role than simply folding lipases, and we identified fibronectin and the low‐density lipoprotein receptor (LDLR) as novel LMF1 clients that contain multiple, non‐sequential disulfide bonds. We conclude that LMF1 is needed for secretion of some ER client proteins that require reduction of non‐native disulfides during their folding.
- Subjects :
- 0301 basic medicine
Proteomics
Protein Folding
Endoplasmic Reticulum
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Homeostasis
Humans
Secretion
Disulfides
Lipase
Molecular Biology
Lipoprotein lipase
General Immunology and Microbiology
biology
General Neuroscience
Endoplasmic reticulum
Membrane Proteins
Articles
Glutathione
Transmembrane protein
Cell biology
Fibronectins
Lipoprotein Lipase
030104 developmental biology
HEK293 Cells
Receptors, LDL
LDL receptor
biology.protein
Protein folding
lipids (amino acids, peptides, and proteins)
Oxidation-Reduction
030217 neurology & neurosurgery
Lipoprotein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....42e5dc5a3f4fe1a1fa39a94bd0906e2e