Lipase maturation factor 1 is required for endothelial lipase activity[S]

Lipase maturation factor 1 (Lmf1) is an endoplasmic reticulum (ER) membrane protein involved in the posttranslational folding and/or assembly of lipoprotein lipase (LPL) and hepatic lipase (HL) into active enzymes. Mutations in Lmf1 are associated with diminished LPL and HL activities (“combined lip...

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Bibliographic Details
Published in:Journal of lipid research 2011-06, Vol.52 (6), p.1162-1169
Main Authors: Ben-Zeev, Osnat, Hosseini, Maryam, Lai, Ching-Mei, Ehrhardt, Nicole, Wong, Howard, Cefalù, Angelo B., Noto, Davide, Averna, Maurizio R., Doolittle, Mark H., Péterfy, Miklós
Format: Article
Language:English
Subjects:
Animals
Chromatography, Affinity
combined lipase deficiency
Electroporation
endoplasmic reticulum
Endoplasmic Reticulum - genetics
Endoplasmic Reticulum - metabolism
Fibroblasts - cytology
Fibroblasts - metabolism
HEK293 Cells
hepatic
Humans
Hypertriglyceridemia - genetics
Hypertriglyceridemia - metabolism
Hypertriglyceridemia - physiopathology
Lipase - genetics
Lipase - metabolism
Lipoprotein Lipase - genetics
Lipoprotein Lipase - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
metabolism
Mice
Mutation
phospholipases
Plasmids
Transfection
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Summary:Lipase maturation factor 1 (Lmf1) is an endoplasmic reticulum (ER) membrane protein involved in the posttranslational folding and/or assembly of lipoprotein lipase (LPL) and hepatic lipase (HL) into active enzymes. Mutations in Lmf1 are associated with diminished LPL and HL activities (“combined lipase deficiency”) and result in severe hypertriglyceridemia in mice as well as in human subjects. Here, we investigate whether endothelial lipase (EL) also requires Lmf1 to attain enzymatic activity. We demonstrate that cells harboring a (cld) loss-of-function mutation in the Lmf1 gene are unable to generate active EL, but they regain this capacity after reconstitution with the Lmf1 wild type. Furthermore, we show that cellular EL copurifies with Lmf1, indicating their physical interaction in the ER. Finally, we determined that post-heparin phospholipase activity in a patient with the LMF1W464X mutation is reduced by more than 95% compared with that in controls. Thus, our study indicates that EL is critically dependent on Lmf1 for its maturation in the ER and demonstrates that Lmf1 is a required factor for all three vascular lipases, LPL, HL, and EL.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M011155