Mechanism of dietary cholesterol uptake by niemann-pick C1-like 1 protein
Abstract/Contents
- Abstract
- Cholesterol is an essential biomolecule playing a number of key physiological roles; disruption of its homeostasis can result in developmental errors, illness or premature death. NPC1L1 plays an important role in cholesterol regulation by mediating its dietary uptake and biliary re-uptake. However, the mechanism of its action and how the drug, Ezetimibe, inhibits NPC1L1 are poorly understood. In this project, we have shown that the existing model that suggested NPC1L1-mediated cholesterol uptake requires endocytosis, and that Ezetimibe works by blocking endocytosis is incorrect. Endocytosis is not involved in NPC1L1-mediated cholesterol uptake or function. We have proposed an alternative, though still incomplete mechanism, based on the similarity between the lysosomal protein NPC1 and NPC1L1. Our data suggest that the N-terminal domain and domain 2 of NPC1L1 require an interaction for both cholesterol uptake and Ezetimibe binding. In addition, we have demonstrated that a functional sterol sensing domain is required for NPC1L1 protein function. Finally, we have shown that microsomal triglyceride transfer protein is involved in regulating the biosynthesis of NPC1L1.
Description
Type of resource | text |
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Form | electronic; electronic resource; remote |
Extent | 1 online resource. |
Publication date | 2017 |
Issuance | monographic |
Language | English |
Creators/Contributors
Associated with | Johnson, Tory A | |
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Associated with | Stanford University, Department of Biochemistry. | |
Primary advisor | Pfeffer, Suzanne | |
Thesis advisor | Pfeffer, Suzanne | |
Thesis advisor | Harbury, Pehr | |
Thesis advisor | Rohatgi, Rajat | |
Advisor | Harbury, Pehr | |
Advisor | Rohatgi, Rajat |
Subjects
Genre | Theses |
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Bibliographic information
Statement of responsibility | Tory A. Johnson. |
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Note | Submitted to the Department of Biochemistry. |
Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Victoria Anne Johnson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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