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Spatial and Functional Aspects of ER-Golgi Rabs and Tethers.

Saraste J - Front Cell Dev Biol (2016)

Bottom Line: Rab1 and Rab2 have numerous effectors or partners that function in membrane tethering, but also have other roles.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Molecular Imaging Center, University of Bergen Bergen, Norway.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: The function of the pcIC as a central trafficking “hub” that is independent from the Golgi stacks is also demonstrated by its close relationship with the endocytic recycling compart-ment (ERC) (Figure 2). Namely, the spatial connection of these compartments, defined by Rab1 and Rab11, respectively, is maintained after Golgi disassembly by BFA and allows the direct exchange (“Golgi bypass”) of certain newly synthesized molecules and internalized plasma membrane receptors between the IC and the endosomal system (Saraste et al., 2009). For example, when the normal recycling of the transferrin receptor from the ERC to the plasma membrane blocked in the presence of BFA, it can return to the cell surface via the pcIC (Marie et al., 2009).


Spatial and Functional Aspects of ER-Golgi Rabs and Tethers.

Saraste J - Front Cell Dev Biol (2016)

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.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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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.
Mentions: The function of the pcIC as a central trafficking “hub” that is independent from the Golgi stacks is also demonstrated by its close relationship with the endocytic recycling compart-ment (ERC) (Figure 2). Namely, the spatial connection of these compartments, defined by Rab1 and Rab11, respectively, is maintained after Golgi disassembly by BFA and allows the direct exchange (“Golgi bypass”) of certain newly synthesized molecules and internalized plasma membrane receptors between the IC and the endosomal system (Saraste et al., 2009). For example, when the normal recycling of the transferrin receptor from the ERC to the plasma membrane blocked in the presence of BFA, it can return to the cell surface via the pcIC (Marie et al., 2009).

Bottom Line: Rab1 and Rab2 have numerous effectors or partners that function in membrane tethering, but also have other roles.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Molecular Imaging Center, University of Bergen Bergen, Norway.

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.

No MeSH data available.


Related in: MedlinePlus