Localization and movement : the yin and yang of membrane trafficking
Abstract/Contents
- Abstract
- Membrane trafficking is an essential process that enables cells to deliver proteins to the extracellular space and segregate proteins into different compartments. Several steps are necessary for the functional segregation and processing of proteins. Trafficking includes post-translational modification of proteins, their movement between compartments, and stable localization once they have reached their target destinations. Importantly, membrane trafficking represents a recursively-sustained system: proteins that play a role in the regulation of membrane trafficking must also be properly transported and localized. Chapter one introduces the importance of the Golgi in the sorting and packaging of proteins and the roles of molecular motors in facilitating individual transport events. To modify transported cargoes, Golgi resident glycosyltransferases need to be localized to the correct cisternae and in some cases, in correct complex with other glycosyltransferases. "Kin recognition", the association of enzymatically compatible glycosyltransferases, has been demonstrated as a mechanism for the stable localization of glycosyltransferases to their proper compartments. Myosins, dyneins, and kinesins, linked to membranes by small Rab GTPases and their effectors, play important roles in moving cargo on actin and microtubule filaments. Their regulation by adapter proteins and their combinatorial interactions both complementing and opposing movement allows for the fine tuning of cargo transport. Chapter two presents the association of UDP-GlcNAc:[beta]Gal [beta]-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) and UDP-Gal:[beta]GlcNAc [beta]-1,4-galactosyltransferase, polypeptide 1 (B4GALT1). These two glycosyltransferases participate in the alternating, successive polymerization of poly-N-acetyllactosamine (polyLacNAc), a linear carbohydrate polymer composed of alternating N-acetylglucosamine and galactose residues. We show that these two glycosyltransferases colocalize by immunofluorescence microscopy, interact by coimmunoprecipitation, and when artificially retained in the ER can retain the complementary glycosyltransferase there as well. Chapter three presents the novel regulation of the KIF3 family kinesin, KIF1C, by small Rab GTPases, Rab1 and Rab6. The depletion of KIF1C impairs the plasma membrane delivery of Vesicular stomatitis virus G protein and intriguingly increases the speed of both Rab1 and Rab6 labeled vesicles. Rab6 can bind directly to the C-terminal domain of KIF1C and, like Rab1, can additionally interact with KIF1C's N-terminal motor domain. The interaction of KIF1C with Rab6 diminishes KIF1C's ability to bind microtubules. These results suggest that KIF1C acts as a brake, perhaps slowing transport to allow proper packaging and tethering to occur. Our data suggest that interaction between Rab6 and KIF1C could relieve KIF1C's braking action by displacing it from microtubules; alternatively, KIF1C may function as a molecular tether between membranes carrying Rab1 and/or Rab6.
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 | Lee, Peter Leader |
|---|---|
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
| Primary advisor | Pfeffer, Suzanne |
| Thesis advisor | Pfeffer, Suzanne |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Meyer, Tobias |
| Thesis advisor | Theriot, Julie |
| Advisor | Ferrell, James Ellsworth |
| Advisor | Meyer, Tobias |
| Advisor | Theriot, Julie |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Peter Leader Lee. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Peter Leader Lee
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