Abstract
Multisubunit tethering complexes (MTCs) positively regulate vesicular fusion by as yet unclear mechanism. In this study we provide evidence that the MTC COG enhances the assembly of fusogenic Golgi SNARE complexes and concomitantly prevents nonfusogenic tSNARE interactions. This capability is possibly mediated by multiple direct interactions of COG subunits and specific Golgi SNAREs and SM (Sec1/Munc18) proteins. By using a systematic co-immunoprecipitation analysis, we identified seven new interactions between the COG subunits and components of the Golgi fusion machinery in mammalian cells. Our studies suggest that these multivalent interactions are critical for the assembly of fusogenic SNARE complexes on the Golgi apparatus and consequently for facilitating endosome-to-trans-Golgi network (TGN) and intra-Golgi retrograde transport, and also for coordinating these transport routes.