Golgi CATCHR complexes function as organizing hubs for vesicle tethering and fusion

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The secretory pathway handles one-third of human proteins, with the Golgi apparatus crucial for their modification and transport.
• Multisubunit tethering complexes, known as CATCHR, are essential for coordinating vesicle docking and fusion.
• CATCHR complexes interact with various trafficking factors including coiled-coil tethers (CCTs), Rab GTPases, SNAREs, and Sec1/Munc18 (SM) proteins.

Purpose of the Study:

• To define the molecular organization of Golgi CATCHR complexes.
• To generate a comprehensive proximity-interaction map of the COG, GARP, and EARP tethering complexes.
• To establish a system-level framework for the spatial organization of Golgi and endosomal membrane trafficking.

Main Methods:

• Utilized functional, near-endogenously expressed TurboID-tagged subunits for proximity-labeling.
• Performed comparative proximity proteomics to map interactions.
• Analyzed interactions with CCTs, Rab-associated proteins, SNAREs, and SM proteins.

Main Results:

• Each CATCHR complex (COG, GARP, EARP) assembles a distinct trafficking module.
• COG preferentially associated with Golgi CCTs and STX5-SCFD1.
• GARP associated with CCDC186 and the STX16-VPS45 pathway; EARP associated with GRIPAP1, CHEVI, and RAB11 machinery.
• Identified CCDC186 as a vesicle tether and WWOX as a regulator of Golgi homeostasis and glycosylation.

Conclusions:

• Golgi CATCHR complexes act as central organizing hubs for specialized trafficking modules.
• These modules coordinate vesicle tethering and membrane fusion events.
• The findings provide a system-level understanding of Golgi and endosomal membrane trafficking regulation.