Structure and mechanism of the blood-brain barrier lipid transporter MFSD2A
Abstract/Contents
- Abstract
- Ion channels and transporters carry out a variety of critical physiological processes, being pivotal in signal transduction, metabolism, and cellular homeostasis. The Major Facilitator Superfamily (MFS) represents the largest group of secondary active transporters identified to date, responsible for translocating numerous diverse substrates. Due to their diverse array of substrates, the MFS proteins represent attractive targets for drug discovery and mechanistic studies. Major facilitator superfamily containing domain 2a (Mfsd2a) is a novel lysolipid transporter within MFS, transporting docosahexanoic acid (DHA) conjugated to lysophosphatidylcholine (LPC), which is crucial for proper brain development. Mfsd2a's lipid transport function has also been found to be key for inhibiting transcytosis at the blood-brain barrier (BBB), ultimately regulating BBB permeability. An exciting possibility raised by this physiological function is modulating Mfsd2a to manipulate BBB permeability for therapeutic treatments. However, a lack of structural information impedes a mechanistic understanding of this key transporter. Herein, I detail the work to determine the cryo-EM structure of Mfsd2a. Based on the Mfsd2a structure, key residues important for activity have also been mapped out in order to improve our understanding of Mfsd2a transport mechanism. The insights into Mfsd2a lipid transport can be leveraged as a foundation to guide future therapeutic development.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Wood, Chase |
|---|---|
| Degree supervisor | Feng, Liang, 1976- |
| Thesis advisor | Feng, Liang, 1976- |
| Thesis advisor | Kobilka, Brian K |
| Thesis advisor | Maduke, Merritt C, 1966- |
| Degree committee member | Kobilka, Brian K |
| Degree committee member | Maduke, Merritt C, 1966- |
| Associated with | Stanford University, Department of Molecular and Cellular Physiology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Chase Alan Wood. |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/vr023fq5143 |
Access conditions
- Copyright
- © 2021 by Chase Wood
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