Discovery of a novel protein complex essential for toxoplasma effector transport into the host cell
Abstract/Contents
- Abstract
- The ability of Toxoplasma to infect and successfully manipulate its host is dependent on its ability to transport "GRA" proteins that originate in unique secretory organelles called dense granules into the host cell in which they reside; however, the essential transport machinery has not been identified. GRAs have diverse roles in Toxoplasma's intracellular lifecycle including co-opting crucial host cell functions and proteins such as the cell cycle, c-Myc and p38 MAP kinase. To identify proteins necessary for the transit of GRAs across the parasitophorous vacuole (PV) membrane, we screened mutants defective in c-Myc upregulation for their ability to export GRA16 and GRA24 to the host cell nucleus as well as modulate host cell processes associated with this and other proteins. This led to the discovery that novel proteins MYR1 (Myc regulation 1), MYR2, and MYR3 play a crucial role in translocation of a subset of GRAs into the host cell. MYR1 is cleaved by ASP5 into two fragments that interact with each other in a disulfide-dependent manner and associate with the PV membranes; interestingly, cleavage is dispensable for MYR1 function. MYR3 likewise associates with PV membranes and co-localizes and interacts with MYR1. Finally, MYR2 is secreted into the PV and associates with PV membranes. Overall, MYR1-3 are the first identified membrane-localized components in Toxoplasma that are required for effector transport across the PVM, and may constitute a novel protein translocon that is essential for hijacking host cell pathways.
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 | Blackburn-Marino, Nicole |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Boothroyd, John C |
| Thesis advisor | Boothroyd, John C |
| Thesis advisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Carette, Jan, 1971- |
| Thesis advisor | Einav, Shirit |
| Thesis advisor | Pringle, John R, 1943- |
| Advisor | Bogyo, Matthew, 1971- |
| Advisor | Carette, Jan, 1971- |
| Advisor | Einav, Shirit |
| Advisor | Pringle, John R, 1943- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Nicole Blackburn-Marino. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Nicole Desiree Blackburn-Marino
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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