Molecular analysis of vesicle tethering at the Golgi
Abstract/Contents
- Abstract
- Mannose 6-phosphate receptors (MPRs) deliver lysosomal acid hydrolases to the endosomal pathway and are then returned from late endosomes to the trans-Golgi network (TGN) for another round of transport. The long coiled-coil protein GCC185 tethers MPR-containing vesicles at the TGN. In the second chapter of this thesis, recent progress in the study of tethers in other laboratories is reviewed. The third chapter describes a mechanism by which GCC185 may tether MPR-containing vesicles. Distinct domains required for the two known functions of this protein, maintenance of Golgi structure and tethering MPR transport vesicles, were identified. The domain needed for vesicle tethering was shown to bind the clathrin adaptor AP-1. Moreover, data are presented showing the presence of AP-1 on transport vesicles en route to the Golgi complex. These data suggest that GCC185, which is localized to the TGN through Arl1- and Rab6-GTPase binding interactions at its C-terminus, engages incoming transport vesicles by binding AP-1 via an internal coiled-coil domain near central, putative "hinge" regions of the protein. Work presented in the fourth chapter describes progress toward understanding the Golgi fragmentation phenotype of cells depleted of GCC185. In addition to the C-terminal localization domain, an N-terminal domain required for Golgi structure maintenance was identified. In addition, GCC185 binding sites for numerous Golgi-localized Rab GTPases were identified, suggesting a model in which GCC185 can make lateral connections across the Golgi ribbon in order to maintain Golgi structure or promote a fused state in the equilibrium between membrane fusion and fission characteristic of the Golgi complex.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Brown, Frank Curtis | |
|---|---|---|
| Associated with | Stanford University, Department of Biochemistry | |
| Primary advisor | Pfeffer, Suzanne | |
| Thesis advisor | Pfeffer, Suzanne | |
| Thesis advisor | Harbury, Pehr | |
| Thesis advisor | Khosla, Chaitan, 1964- | |
| Advisor | Harbury, Pehr | |
| Advisor | Khosla, Chaitan, 1964- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Frank Curtis Brown. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Frank Curtis Brown
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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