Molecular mechanism of pathogenic LRRK2 membrane recruitment
Abstract/Contents
- Abstract
- Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson's disease and we showed previously that activated LRRK2 phosphorylates a subset of Rab GTPases. Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. Here we define the Rab29 binding region of the LRRK2 Armadillo domain and show that it can also bind additional LRRK2 substrates, Rab8A and 10. Moreover, we identify a distinct and higher affinity interaction interface between phosphorylated Rab8 and Rab10 within LRRK2's N-terminus that can retain LRRK2 on membranes in cells to catalyze multiple phosphorylation events. These findings reveal a feed-forward pathway that provides spatial control and apparent membrane activation of LRRK2 kinase activity.
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 | Vides, Edmundo Gabriel |
|---|---|
| Degree supervisor | Pfeffer, Suzanne |
| Thesis advisor | Pfeffer, Suzanne |
| Thesis advisor | Harbury, Pehr |
| Thesis advisor | Straight, Aaron, 1966- |
| Degree committee member | Harbury, Pehr |
| Degree committee member | Straight, Aaron, 1966- |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Edmundo G. Vides. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/cp247th0446 |
Access conditions
- Copyright
- © 2021 by Edmundo Gabriel Vides
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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