Membrane trafficking is the process of organized transport of secretory and transmembrane proteins in the cell. This transport is highly regulated and requires the concerted actions of many trafficking machinery proteins. One such member of these trafficking regulatory proteins is the COG or conserved oligomeric Golgi complex. The COG complex is a multi-subunit tethering factor that is necessary for the tethering and organization of retrograde intra-Golgi vesicles recycling glycosylation enzymes. The COG complexes is evolutionarily conserved and COG mutations have been directly linked to physiological abnormalities including congenital disorders of glycosylation.
The COG complex has been shown to interact with many different trafficking machinery proteins, including SNARE proteins. Previous studies of COG-SNARE interactions demonstrated that the COG complex promotes and stabilizes SNARE complex formation for the Golgi localized Syntaxin5 (STX5)- containing SNARE complex. We used a systematic approach to fully characterize COG-SNARE interactions and found that, indeed, COG regulates two different SNARE complexes (STX5- and STX16- containing SNARE complexes), and serves as a landmark in the delivery of these SNAREs to their target membrane.
The COG complex is comprised of eight different proteins organized into two lobes, termed lobe A and lobe B. Genetic and phenotypic differences between lobe A and lobe B subunits suggest lobe A and lobe B are separate sub-complexes in the cell. We demonstrated that indeed lobe A and lobe B are stable sub-complexes and appear to have distinct functional characteristics. Additionally, we demonstrated that lobe A and lobe B subunits are readily present on different membranes.
We combine these data to propose a mechanistic model of COG mediated vesicle tethering. We conclude that bi-lobed bridging of lobe A and lobe B on opposing membranes confers the vesicle tethering function of the COG complex.
|Advisor:||Lupashin, Vladimir V.|
|Commitee:||Gaddy, Dana, Morello, Ray, Storrie, Brian, Voth, Daniel|
|School:||University of Arkansas for Medical Sciences|
|Department:||Physiology and Biophysics|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 76/09(E), Dissertation Abstracts International|
|Keywords:||Conserved oligomeric golgi complex, Golgi, Membrane trafficking, Snares, Sub-complex, Tethering|
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