Role of GARP Vesicle Tethering Complex in Golgi Physiology

Abstract

The Golgi associated retrograde protein complex (GARP) is an evolutionarily conserved component of Golgi membrane trafficking machinery that belongs to the Complexes Associated with Tethering Containing Helical Rods (CATCHR) family. Like other multisubunit tethering complexes such as COG, Dsl1, and Exocyst, the GARP is believed to function by tethering and promoting fusion of the endosome-derived small trafficking intermediate. However, even twenty years after its discovery, the exact structure and the functions of GARP are still an enigma. Recent studies revealed novel roles for GARP in Golgi physiology and identified human patients with mutations in GARP subunits. In this review, we summarized our knowledge of the structure of the GARP complex, its protein partners, GARP functions related to Golgi physiology, as well as cellular defects associated with the dysfunction of GARP subunits.

Golgi-associated retrograde protein (GARP) complex recruits retromer to trans-Golgi network for FgKex2 and FgSnc1 recycling, necessary for development and pathogenicity ofFusarium graminearum

“…A previous research has established that Vps51 predominantly localizes to the TGN in yeast 14 . In our investigation of the localization of FgVps51-GFP in F. graminearum , we found that the FgVps51-GFP primarily exhibited a punctate cytoplasmic distribution at various developmental stages, ranging from conidiogenesis (from phialides to mature conidia) to germination (from germlings to vegetative hyphae).…”

“…Apart from Vps51, the yeast GARP complex comprises three additional vacuolar protein sorting proteins namely Vps52, Vps53 and Vps54 which also localize primarily in the TGN 14,20 . To identify the homologues of these three GARP complex subunits in F. graminearum genome, we carried out BLASTp analyses of their respective protein sequences in yeast against the F. graminearum genome.…”

“…The tethering factor plays a pivotal role in initiating contact between the transport vesicles and the receptor membrane 10,13 . It identifies the transport vesicles and brings them to close contact with the receptor membrane 14 . During this process, the tethering factor, in conjunction with small GTPases and their downstream partners, interacts with some SNARE proteins to collectively regulate the membrane fusion process 15,16 .…”

“…Presently, there are a total of ten multi-subunit tethered complexes, strategically positioned within different transport pathways, each carrying out its distinct regulatory functions 17,18 . Among these, the Golgi-associated retrograde protein (GARP) complex primarily resides within the trans-Golgi network (TGN), functioning as a tethering factor that mediates retrograde transport from endosomes to the TGN 14,19 .…”

“…As a heteromeric protein complex, it consists of four distinct subunits: vacuolar protein sorting 51 (VPS51), VPS52, VPS53 and VPS54 21 . The GARP complex plays a crucial role in the tethering transport vesicles with the TGN, ultimately facilitating the fusion between the vesicles and the receptor membranes 14 . Fusion of transport vesicles with the TGN is instrumental in promoting the recycling of various membrane proteins, such as the vacuolar protein sorting receptor Vps10 22 , the cell wall sensor Wsc1 23 .…”