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

First Author  Pérez-Victoria FJ Year  2009
Journal  Mol Cell Biol Volume  29
Issue  19 Pages  5251-63
PubMed ID  19620288 Mgi Jnum  J:153910
Mgi Id  MGI:4366602 Doi  10.1128/MCB.00495-09
Citation  Perez-Victoria FJ, et al. (2009) Dual roles of the mammalian GARP complex in tethering and SNARE complex assembly at the trans-golgi network. Mol Cell Biol 29(19):5251-63
abstractText  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 (GARP) complex regulates retrograde transport from endosomes to the trans-Golgi network (TGN). Although GARP 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 GARP 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 GARP functions upstream of the SNAREs, regulating their localization and assembly into SNARE complexes. However, interactions of GARP with SNAREs are insufficient to promote retrograde transport, because deletion of the C-terminal region of Vps53 precludes GARP function without affecting GARP-SNARE interactions. Finally, we present in vitro data consistent with a tethering role for GARP, which is disrupted by deletion of the Vps53 C-terminal region. These findings indicate that GARP 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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