Role of the Conserved Ologomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

摘要

The conserved oligomeric Golgi (COG) complex was identified as one of the evolutionary conserved protein complexes that regulate a cis-Golgi step in intracellular vesicular transport. This evolutionary conserved complex is composed of eight subunits. Mutations in the COG complex subunits result in defects in basic Golgi functions: glycosylation of secretory proteins, protein sorting and retention of Golgi resident proteins. We propose that the COG3 protein plays one of the main roles in these processes. We utilized RNA interference assay to knockdown COG3p in HeLa cells to determine the effect of its depletion on Golgi proteins localization. siRNA dependent Cog3 depletion causes rapid Golgi fragmentation and possibly accumulation of Golgi resident proteins in transport vesicles. Furthermore in COG3 depleted cells level of COG1, 2, 4 and 8 is also reduced while the level of COG5 and 6 subunits is not changed. We found that the COG complex physically interacts with components of intra-Golgi trafficking machinery including v-SNARE GS28. COG3 protein is localized on Golgi in normal conditions but in breast cancer cells in addition to the Golgi it is also found on peripheral structures where it is colocalized with SNARE protein GS28. We concluded that mammalian COG complex serves as a 'docking station' for retrograde intra-Golgi vesicles and that the lobe A of COG complex (subunits 1-4) is essential for this process. These results help to further define the COG complex function in protein trafficking.