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 |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Johnson, Tory A |
|---|---|
| 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 |
|---|
Bibliographic information
| Statement of responsibility | Tory A. Johnson. |
|---|---|
| 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).
Also listed in
Loading usage metrics...