Molecular insights into vesicle tethering at the Golgi by the Conserved Oligomeric Golgi (COG) complex and the golgin TMF

TY - JOUR

T1 - Molecular insights into vesicle tethering at the Golgi by the Conserved Oligomeric Golgi (COG) complex and the golgin TMF

AU - Miller, Victoria J

AU - Sharma, Prateek

AU - Kudlyk, Tetyana A

AU - Frost, Laura

AU - Rofe, Adam P

AU - Watson, Irene J

AU - Duden, Rainer

AU - Lowe, Martin

AU - Lupashin, Vladimir V

AU - Ungar, Daniel

PY - 2013/2/8

Y1 - 2013/2/8

N2 - Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyse the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The found interactions of COG's subunits with members of transport factor families assign the individual subunits as specific interaction hubs. Functional analysis of selected interactions suggests a mechanistic tethering model. We find that the COG complex interacts with two different Rabs in addition to each end of the golgin "TATA element modulatory factor" (TMF). This allows COG to potentially bridge the distance between the golgin's distal end and the target membrane thereby promoting tighter docking. Concurrently we show that the central portion of TMF can bind to Golgi membranes that are liberated of their COPI cover. This latter interaction could serve to bring vesicle and target membranes into close apposition prior to fusion. A target selection mechanism, in which a hetero-oligomeric tethering factor organises Rabs and coiled transport factors to enable protein sorting specificity, could be applicable to vesicle targeting throughout eukaryotic cells.

AB - Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyse the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The found interactions of COG's subunits with members of transport factor families assign the individual subunits as specific interaction hubs. Functional analysis of selected interactions suggests a mechanistic tethering model. We find that the COG complex interacts with two different Rabs in addition to each end of the golgin "TATA element modulatory factor" (TMF). This allows COG to potentially bridge the distance between the golgin's distal end and the target membrane thereby promoting tighter docking. Concurrently we show that the central portion of TMF can bind to Golgi membranes that are liberated of their COPI cover. This latter interaction could serve to bring vesicle and target membranes into close apposition prior to fusion. A target selection mechanism, in which a hetero-oligomeric tethering factor organises Rabs and coiled transport factors to enable protein sorting specificity, could be applicable to vesicle targeting throughout eukaryotic cells.

UR - http://www.scopus.com/inward/record.url?scp=84873630243&partnerID=8YFLogxK

U2 - 10.1074/jbc.M112.426767

DO - 10.1074/jbc.M112.426767

M3 - Article

C2 - 23239882

SN - 0021-9258

VL - 288

SP - 4229

EP - 4240

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 6

ER -