Dual roles of the mammalian GARP complex in tethering and SNARE complex assembly at the trans-golgi network.

Tethering factors and SNAREs control the last two steps of vesicular trafficking: the initial interaction and the fusion, respectively, of transport vesicles with target membranes. The Golgi-associated retrograde protein complex regulates retrograde transport from endosomes to the trans-Golgi network (TGN). Although has been proposed to function as a tethering factor at the TGN, direct evidence for such a role is still lacking. Herein we report novel and specific interactions of the mammalian Gduanyu37 complex with SNAREs that participate in endosome-to-TGN transport, namely, syntaxin 6, syntaxin 16, and Vamp4. These interactions depend on the N-terminal regions of Vps53 and Vps54 and the SNARE motif of the SNAREs. We show that Gduanyu37 functions upstream of the SNAREs, regulating their localization and assembly into SNARE complexes. However, interactions of Gduanyu37 with SNAREs are insufficient to promote retrograde transport, because deletion of the C-terminal region of Vps53 precludes Gduanyu37 function without affecting interactions. Finally, we present in vitro data consistent with a tethering role for which is disrupted by deletion of the Vps53 C-terminal region. These findings indicate that Gduanyu37 orchestrates retrograde transport from endosomes to the TGN by promoting vesicle tethering and assembly of SNARE complexes in consecutive, independent steps.

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