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Review
. 2023 Mar 23;24(7):6069.
doi: 10.3390/ijms24076069.

Role of GARP Vesicle Tethering Complex in Golgi Physiology

Amrita Khakurel  1 , Vladimir V Lupashin  1
Affiliations
Review

Role of GARP Vesicle Tethering Complex in Golgi Physiology

Amrita Khakurel et al. Int J Mol Sci. .

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.

Keywords: GARP complex; Golgi; SNARE; glycosylation; vesicle tethering.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of the GARP complex. (A) Schematic representation of the proposed 3D structure of yeast GARP complex based on negative-stain electron microscopy [11]. (B) AlphaFold structure prediction of human GARP complex. The N-terminal regions of VPS51 (1–194), VPS52 (1–178), VPS53 (1–169), and VPS54 (1–310) were used to assemble a 3D core structure of the GARP complex using the ColabFold [20] plugin of the UCSF ChimeraX program [21]. AlphaFold predicted 3D structures of individual subunits were fitted to the core structure using the “matchmaker” command of the UCSF ChimeraX program, and the resulting structures were colored using the Rainbow palette. Scale bar is 10 nm. Predicted 3D structures of individual VPS51-54 human proteins were updated in AlphaFold DB version 2022-11-01, created with the AlphaFold Monomer v2.0 pipeline. The predicted 3D structure of the GARP complex was assembled on 27 December 2022 and colored using ChimeraX.
Figure 2
Figure 2
GARP is localized to trans-Golgi/TGN in human cells. hTERT–RPE1 VPS54 knock out cells stably expressing mVPS54–13myc were stained with antibodies to TGN protein TGN46, cis/medial Golgi protein Giantin and myc (VPS54). Airyscan super-resolution images (MIPs of 14 z-stack) were collected with 63x oil 1.4 NA objective on Zeiss LSM880.
Figure 3
Figure 3
Cartoon depicting the predicted role of the GARP complex and other trafficking components in the tethering of endosome-derived vesicles to the TGN. (A) Cargo selection: Recycling soluble and transmembrane cargo molecules such as the mannose-6-phosphate receptor and TGN46 are selected and packaged in the trafficking intermediates (vesicle) using ARF1 GTPase and a vesicular coat (AP1, GGA or COPI). (B) Budding: After the vesicle is formed, it is budded off the endosomal compartment. (C) Uncoating: ARF1 hydrolyzes GTP, and the coat gradually falls off. (D) Initial capture: Once the vesicle reaches proximity to the TGN, coiled-coil tethers (Golgin97, Golgin245, and GCC185) perform the initial capture. (E) Tethering by GARP: GARP complex binds coiled-coil tethers and SNAREs to control and coordinate docking of the vesicle with the TGN membrane. (F) Fusion: Following the tethering by the GARP complex, the trans-SNARE complex is formed, which results in vesicle fusion with the TGN to deliver the recycling molecules.
Figure 4
Figure 4
GARP dysfunction results in the depletion and mislocalization of multiple Golgi proteins, altering Golgi homeostasis. (Left) A schematic of Golgi proteins in wild type cells. (Right) GARP deficient cells are depleted for multiple resident Golgi proteins. COPI coats and ARFGAP1 are mislocalized to ERGIC., while BIG1 is relocated to endolysosomal compartments.
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References

    1. Conibear E., Stevens T.H. Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol. Biol. Cell. 2000;11:305–323. doi: 10.1091/mbc.11.1.305. - DOI - PMC - PubMed
    1. Conboy M.J., Cyert M.S. Luv1p/Rki1p/Tcs3p/Vps54p, a yeast protein that localizes to the late Golgi and early endosome, is required for normal vacuolar morphology. Mol. Biol. Cell. 2000;11:2429–2443. doi: 10.1091/mbc.11.7.2429. - DOI - PMC - PubMed
    1. Siniossoglou S., Pelham H.R.B. Vps51p links the VFT complex to the SNARE Tlg1p. J. Biol. Chem. 2002;277:48318–48324. doi: 10.1074/jbc.M209428200. - DOI - PubMed
    1. Conibear E., Cleck J.N., Stevens T.H. Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlg1p. Mol. Biol. Cell. 2003;14:1610–1623. doi: 10.1091/mbc.e02-10-0654. - DOI - PMC - PubMed
    1. Reggiori F., Wang C.-W., Stromhaug P.E., Shintani T., Klionsky D.J. Vps51 is part of the yeast Vps fifty-three tethering complex essential for retrograde traffic from the early endosome and Cvt vesicle completion. J. Biol. Chem. 2003;278:5009–5020. doi: 10.1074/jbc.M210436200. - DOI - PMC - PubMed

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