THE ROLE OF LIPASE MATURATION FACTOR 1 IN THE MATURATION OF LIPOPROTEIN LIPASE Public Deposited

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  • March 20, 2019
Creator
  • Babilonia-Rosa, Melissa
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Abstract
  • Over a third of the US adult population has elevated blood triglyceride (TG) levels (hypertriglyceridemia), resulting in an increased risk of atherosclerosis, pancreatitis, and metabolic syndrome. Lipases are responsible for lipid uptake from dietary sources and for the distribution of fatty acids to different tissues. Lipoprotein lipase (LPL), a dimeric enzyme, is the main lipase responsible for TG clearance from the blood after food intake. In difference of monomeric lipases, dimeric lipases require lipase maturation factor 1 (LMF1) for proper folding, activity, and secretion. LMF1 is a transmembrane protein located in the endoplasmic reticulum (ER). Although LMF1 is crucial for ER exit of dimeric lipases, the mechanism by which LMF1 promotes lipase maturation is not known. My thesis work aims to understand LMF1's role in LPL maturation using cell biology and biochemical methods. I have developed N-terminal truncation mutants of LMF1, which revealed that full length LMF1 is required for the maturation of LPL. We employed LMF1-crosslinking/mass spectrometry studies to identify proteins with a role in LPL maturation. Our novel interacting partners of LMF1 and LPL were validated by pull down assays and by protein knockdowns to assess effects on LPL maturation. We found five novel, ER-resident binding partners of LMF1. Three of these proteins are involved in formation and isomerization of disulfide bonds. Given the role in oxidative folding of most of the new partners we propose that LMF1 promotes LPL folding by promoting redox homeostasis in the ER.
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Rights statement
  • In Copyright
Advisor
  • Coleman, Rosalind
  • Kuhlman, Brian
  • Dohlman, Henrik
  • Neher, Saskia
  • Maddox, Amy
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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