The COG complex interacts directly with Syntaxin 6 and positively regulates endosome-to-TGN retrograde transport.

The COG complex interacts directly with Syntaxin 6 and positively regulates endosome-to-TGN retrograde transport.
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DOI:
10.1083/jcb.201102045
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发表时间:
2011-08-08
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lev S
Lev S
中科院分区:
其他
文献类型:
--
作者:
Laufman O;Hong W;Lev S

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保守的低聚高尔基体 (COG) 复合体与 t-SNARE Syntaxin 6 相互作用,促进内体到 TGN 的逆行运输。在酵母和哺乳动物中,保守的寡聚高尔基体 (COG) 复合体参与调节内体到反高尔基体网络 (TGN) 的逆行运输。然而,它调节这条运输路线的确切机制仍然很大程度上未知。在本文中,我们证明 COG 通过 Cog6 亚基直接与靶膜 SNARE (t-SNARE) Syntaxin 6 相互作用。在 Cog6 耗尽的细胞中,突触蛋白 6 的稳态水平显着降低,同时,内体到 TGN 的逆行交通显着减弱。 Cog6 敲低还影响 Syntaxin 16、Vti1a 和 VAMP4 的稳态水平和/或亚细胞分布,并损害 Syntaxin 6-Syntaxin16-Vti1a-VAMP4 SNARE 复合物的组装。值得注意的是,VAMP4 的过表达(而非 Syntaxin 6 的过表达)绕过了对 COG 的需求,并在 Cog6 耗尽的细胞中恢复了内体到 TGN 的运输。这些结果表明,COG 直接与特定的 t-SNARE 相互作用,并积极调节 SNARE 复合物的组装,从而影响其相关的运输步骤。
The conserved oligomeric Golgi (COG) complex interacts with the t-SNARE Syntaxin 6 and promotes endosome-to-TGN retrograde trafficking. 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.
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