title: The COG complex interacts directly with Syntaxin 6 and positively regulates endosome-to-TGN retrograde transport.
abstract: The conserved oligomeric Golgi (COG) complex has been implicated in the regulation of endosome to trans-Golgi network (TGN) retrograde trafficking in both yeast and mammals. However, the exact mechanisms by which it regulates this transport route remain largely unknown. In this paper, we show that COG interacts directly with the target membrane SNARE (t-SNARE) Syntaxin 6 via the Cog6 subunit. In Cog6-depleted cells, the steady-state level of Syntaxin 6 was markedly reduced, and concomitantly, endosome-to-TGN retrograde traffic was significantly attenuated. Cog6 knockdown also affected the steady-state levels and/or subcellular distributions of Syntaxin 16, Vti1a, and VAMP4 and impaired the assembly of the Syntaxin 6-Syntaxin16-Vti1a-VAMP4 SNARE complex. Remarkably, overexpression of VAMP4, but not of Syntaxin 6, bypassed the requirement for COG and restored endosome-to-TGN trafficking in Cog6-depleted cells. These results suggest that COG directly interacts with specific t-SNAREs and positively regulates SNARE complex assembly, thereby affecting their associated trafficking steps.
authors.affiliation: Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Laufman
authors.forename: WanJin
authors.initials: W
authors.lastname: Hong
authors.forename: Sima
authors.initials: S
authors.lastname: Lev
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000032:analysis / Q000378:metabolism*; D050766:Qb-SNARE Proteins / Q000032:analysis / Q000378:metabolism; D050683:R-SNARE Proteins / Q000032:analysis / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051438:Syntaxin 16 / Q000032:analysis / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C553748:COG6 protein, human; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; D051438:Syntaxin 16; C476456:VAMP4 protein, human; C491419:VTI1A protein, human; D033921:Vesicular Transport Proteins