Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 18:4:28.
doi: 10.3389/fcell.2016.00028. eCollection 2016.

Spatial and Functional Aspects of ER-Golgi Rabs and Tethers

Jaakko Saraste  1
Affiliations

Spatial and Functional Aspects of ER-Golgi Rabs and Tethers

Jaakko Saraste. Front Cell Dev Biol. .

Abstract

Two conserved Rab GTPases, Rab1 and Rab2, play important roles in biosynthetic-secretory trafficking between the endoplasmic reticulum (ER) and the Golgi apparatus in mammalian cells. Both are expressed as two isoforms that regulate anterograde transport via the intermediate compartment (IC) to the Golgi, but are also required for transport in the retrograde direction. Moreover, Rab1 has been implicated in the formation of autophagosomes. Rab1 and Rab2 have numerous effectors or partners that function in membrane tethering, but also have other roles. These include the coiled-coil proteins p115, GM130, giantin, golgin-84, and GMAP-210, as well as the multisubunit COG (conserved oligomeric Golgi) and TRAPP (transport protein particle) tethering complexes. TRAPP also acts as the GTP exchange factor (GEF) in the activation of Rab1. According to the traditional view of the IC elements as motile, transient structures, the functions of the Rabs could take place at the two ends of the ER-Golgi itinerary, i.e., at ER exit sites (ERES) and/or cis-Golgi. However, there is considerable evidence for their specific association with the IC, including its recently identified pericentrosomal domain (pcIC), where many of the effectors turn out to be present, thus being able to exert their functions at the pre-Golgi level. The IC localization of these proteins is of particular interest based on the imaging of Rab1 dynamics, indicating that the IC is a stable organelle that bidirectionally communicates with the ER and Golgi, and is functionally linked to the endosomal system via the pcIC.

Keywords: ER-Golgi transport; Golgi apparatus; Rab1; Rab2; endocytic recycling compartment; golgins; pre-Golgi intermediate compartment; tethering factors.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Confocal microscopic localization of the two Rab1 isoforms and the effectors of Rab1 (p115, GM130) and Rab2 (GM130, GMAP210) that have been suggested to function in membrane tethering in the early secretory pathway. Normal rat kidney (NRK) cells stably expressing GFP-Rab1A (Marie et al., 2009) were stained with antibodies against Rab1B, p115, GM130, or GMAP210. The images show cells in which the pcIC, an extensive tubular network under the nucleus (large arrowheads), has separated from the Golgi ribbon concomitantly with the movement of the centrosome to the cell center. Rab1A and B display similar localizations; that is, in addition to the Golgi ribbon they both associate with the pcIC, as well as with peripheral IC elements in the vicinity of ERES (small arrowheads). It should be noted that Rab1A and the tethering factors display variable overlap in the pcIC, suggesting their association with its different subdomains. Bars: 10 μm.
Figure 2
Figure 2
Different models on the organization of the ER-Golgi interface and the functions of Rab1 or Rab2 effectors (bold) or Rab1 GEFs (TRAPPs) in trafficking. Two alternative pathways connecting the peripheral ERES and the Golgi stacks (green) are shown (A and B), while Golgi-adjacent ERES is a common feature of both models. The pcIC is depicted as a separate entity (see Figure 1), since its normal dynamic relationship with the Golgi apparatus remains unknown. At ERES, homotypic fusion of ER-derived COPII vesicles or their heterotypic fusion with the IC elements involve TRAPPI and p115, the GEF, and effector of Rab1, respectively. However, it should be noted that the TRAPPI complex in mammalian cells remains enigmatic. (A) Traditionally, IC-to-Golgi transport is viewed as a one-step process based on MT-based direct movement of IC elements from peripheral ERES to the cis-Golgi region, where they undergo homotypic fusion to generate new Golgi cisternae in a process that may involve e.g., GM130, an effector of both Rab1 and Rab2. Instead of operating in IC or cis-Golgi events many of the Rab1 effectors (such as COG, giantin, and golgin-84) could play a role in intra-Golgi trafficking. (B) An alternative model presenting the IC as a dynamic membrane network, which is stably anchored next to the centrosome. Accordingly, transport from peripheral ERES to the Golgi is a two-step process via the pcIC, opening for possible new roles for Rab1, Rab2 and their effectors. These include homotypic fusion of pcIC elements (GM130), retrograde transport from the pcIC to peripheral ERES (GMAP-210), and two-way trafficking between the pcIC and the Golgi stacks (p115, giantin, golgin-84, COG), as well as between pcIC and the ERC (TRAPPIII). The Rab1 isoforms are expected to be present throughout the IC network (blue), while the localization of the Rab2 isoforms is less well known. For simplicity, the endosomal connection is not included in model A. The inset (bottom left) depicts a basic IC element, showing differential association of Rab1A and Rab1B with its tubular and saccular (vacuolar) membrane domains, raising the possibility that Rab1 effectors, such as p115 and GM130, may display non-overlapping distributions within these elements.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aizawa M., Fukuda M. (2015). Small GTPase Rab2B and its specific binding protein Golgi-associated Rab2B interactor-like 4 (GARI-L4) regulate Golgi morphology. J. Biol. Chem. 290, 22250–22261. 10.1074/jbc.M115.669242 - DOI - PMC - PubMed
    1. Allan B. B., Moyer B. D., Balch W. E. (2000). Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science 289, 444–448. 10.1126/science.289.5478.444 - DOI - PubMed
    1. Alvarez C., Fujita H., Hubbard A., Sztul E. (1999). ER to Golgi transport: requirement for p115 at a pre-Golgi VTC stage. J. Cell Biol. 147, 1205–1222. 10.1083/jcb.147.6.1205 - DOI - PMC - PubMed
    1. Alvarez C., Garcia-Mata R., Brandon E., Sztul E. (2003). COPI recruitment is modulated by a Rab1b-dependent mechanism. Mol. Biol. Cell 14, 2116–2127. 10.1091/mbc.E02-09-0625 - DOI - PMC - PubMed
    1. Alvarez C., Garcia-Mata R., Hauri H.-P., Sztul E. (2001). The p115-interactive proteins GM130 and giantin participate in endoplasmic reticulum-Golgi traffic. J. Biol. Chem. 276, 2693–2700. 10.1074/jbc.M007957200 - DOI - PubMed

LinkOut - more resources