The Golgi puppet master: COG complex at center stage of membrane trafficking interactions

Abstract

The central organelle within the secretory pathway is the Golgi apparatus, a collection of flattened membranes organized into stacks. The cisternal maturation model of intra-Golgi transport depicts Golgi cisternae that mature from cis to medial to trans by receiving resident proteins, such as glycosylation enzymes via retrograde vesicle-mediated recycling. The conserved oligomeric Golgi (COG) complex, a multi-subunit tethering complex of the complexes associated with tethering containing helical rods family, organizes vesicle targeting during intra-Golgi retrograde transport. The COG complex, both physically and functionally, interacts with all classes of molecules maintaining intra-Golgi trafficking, namely SNAREs, SNARE-interacting proteins, Rabs, coiled-coil tethers, vesicular coats, and molecular motors. In this report, we will review the current state of the COG interactome and analyze possible scenarios for the molecular mechanism of the COG orchestrated vesicle targeting, which plays a central role in maintaining glycosylation homeostasis in all eukaryotic cells.

Figure 1

COG complex interactome defines subunit specific hubs of regulated trafficking related proteins. A comprehensive map of interactions between COG subunits and different trafficking related proteins. COG subunits can be classified by the groups of trafficking proteins that they interact with including SNAREs (blue), tethers (purple), Rabs (yellow) and coat and motor proteins (maroon). In this organization scheme we define the COG subunits as hubs for the class of protein that they interact with. COG subunits COG2 and COG3 are defined as “tether hubs”, COG2 COG3 and COG4 are defined as “coat and motor hubs”, COG4, COG5, and COG6 are defined as “Rab hubs”, and COG4, COG6, COG7, and COG8 are defined as “SNARE hubs”. Interestingly, COG1 has no other specific interactions therefore it is designated as the critical subunit for maintaining the structural integrity of the entire complex.

Figure 2

The COG complex assembles docking stations for retrograde intra-Golgi vesicles Hypothetical model depicting how the COG complex may serve to assemble docking stations on Golgi membranes for incoming retrograde vesicles. In this model the COG complex (or COG sub-complexes) act to orchestrate the assembly of a pre-tethering protein complex through interactions with Rabs, coiled-coil tethers, and SNAREs. The targeting of a vesicle in this model is defined by the specific COG interactions, meaning the Rab, SNARE, or tether that are assembled into the docking complex.

Figure 3

The COG complex directly facilitates vesicle tethering Hypothetical model depicting how the COG complex may act to directly facilitate the tethering of a retrograde vesicle with its acceptor membrane. In this model, the interactions between COG subunits and trafficking proteins carried on an incoming vesicle (for example v-SNAREs, Rabs, and/or coat proteins) would establish a connection between the vesicle and an acceptor membrane. Additionally, COG interactions could also serve to shorten or even stabilize the connection between the vesicle and the acceptor membrane achieved by long coiled-coil tethers.

Figure 4

The COG complex stabilizes SNARE complexes Hypothetical model depicting how the COG complex may assist in the stabilization of t-t and or v-t SNARE complexes. In this model multiple COG subunits interacting with the same SNARE complex (COG4-STX5, COG6-GS27, and COG7-GS28 interactions with the STX5/GS27/GS28/GS15 SNARE complex and COG6-STX6, COG8-STX16, and COG4-Vti1a interactions with the STX16/STX6/Vti1a/Vamp4 SNARE complex) may act to stabilize the complex and protect it from NSF mediated disassembly. Furthermore, interactions between COG subunits and SM proteins may aid in the COG mediated stabilization of SNARE complexes.