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Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is dynamically localized to the Golgi apparatus by coatomer.

Sato K, Sato M, Nakano A - J. Cell Biol. (2001)

Bottom Line: Either a lesion of coatomer or deletion of the COOH-terminal tail of Rer1p causes its mislocalization to the vacuole.The COOH-terminal Rer1p tail interacts in vitro with a coatomer complex containing alpha and gamma subunits.These findings not only give the proof that Rer1p is a novel type of retrieval receptor recognizing the TMD in the Golgi but also indicate that coatomer actively regulates the function and localization of Rer1p.

View Article: PubMed Central - PubMed

Affiliation: Molecular Membrane Biology Laboratory, RIKEN (The Institute of Physical and Chemical Research), Saitama 351-0198, Japan. satoken@postman.riken.go.jp

ABSTRACT
Rer1p, a yeast Golgi membrane protein, is required for the retrieval of a set of endoplasmic reticulum (ER) membrane proteins. We present the first evidence that Rer1p directly interacts with the transmembrane domain (TMD) of Sec12p which contains a retrieval signal. A green fluorescent protein (GFP) fusion of Rer1p rapidly cycles between the Golgi and the ER. Either a lesion of coatomer or deletion of the COOH-terminal tail of Rer1p causes its mislocalization to the vacuole. The COOH-terminal Rer1p tail interacts in vitro with a coatomer complex containing alpha and gamma subunits. These findings not only give the proof that Rer1p is a novel type of retrieval receptor recognizing the TMD in the Golgi but also indicate that coatomer actively regulates the function and localization of Rer1p.

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Model of the dynamic function of Rer1p. Rer1p recognizes the signal in the TMD of cargo proteins and actively recycles between the early Golgi and the ER. When it is mislocalized to the late Golgi, it is retrieved to the early Golgi by the COPI vesicles (solid arrows). In COPI mutants, Rer1p is no longer able to localize to the Golgi and is transported to the vacuole via the MVB sorting pathway (broken arrows).
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Figure 7: Model of the dynamic function of Rer1p. Rer1p recognizes the signal in the TMD of cargo proteins and actively recycles between the early Golgi and the ER. When it is mislocalized to the late Golgi, it is retrieved to the early Golgi by the COPI vesicles (solid arrows). In COPI mutants, Rer1p is no longer able to localize to the Golgi and is transported to the vacuole via the MVB sorting pathway (broken arrows).

Mentions: The purpose of this study is to demonstrate that Rer1p is a sorting receptor in the cis-Golgi which recognizes signals present in TMDs of a set of ER membrane proteins and retrieves them to the ER (Fig. 7). We have shown the first biochemical evidence for the direct interaction between Rer1p and the TMD of Sec12p (Fig. 1). The following observations support the role of Rer1p as a receptor. First, the TMDs of Sec12p, Sed4p, and Gas1p contain information for the Rer1p-dependent retrieval to the ER, and the spatial locations of polar residues in these TMDs are important for the recognition by Rer1p (Sato et al. 1996; Letourneur and Cosson 1998; Sato, K., and A. Nakano, unpublished data). Second, there is an apparent competition for Rer1p between Sec12p and Sec71p, suggesting a saturable mechanism for the retrieval (Sato et al. 1997). Rer1p is a limiting component in this competition. We have also demonstrated that coatomer plays a critical role for the function and localization of Rer1p. Mfα1p fusions of Sec12p, Sec71p, and Sec63p whose correct ER localization depends on Rer1p are all mislocalized to the trans-Golgi in an α-COP mutant (Sato et al. 1997). Rer1p itself is vigorously recycling between the Golgi and the ER in a COPI-dependent fashion (Fig. 3 and Fig. 6 c) and is mistargeted to the vacuole in α-, β′-, and γ-COP mutants (Fig. 6, a and b). Most importantly, coatomer subunits bind to the COOH-terminal tail of Rer1p in vitro (Fig. 6 e). All of these observations led us to conclude that Rer1p is a novel type of receptor that recognizes a retrieval signal in the lipid bilayer. Such a ligand–receptor interaction in the lipid milieu has been long proposed to explain membrane protein sorting. The binding of Rer1p with the Sec12p TMD would provide an ideal example to study the mode of interaction from a structural viewpoint as well.


Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is dynamically localized to the Golgi apparatus by coatomer.

Sato K, Sato M, Nakano A - J. Cell Biol. (2001)

Model of the dynamic function of Rer1p. Rer1p recognizes the signal in the TMD of cargo proteins and actively recycles between the early Golgi and the ER. When it is mislocalized to the late Golgi, it is retrieved to the early Golgi by the COPI vesicles (solid arrows). In COPI mutants, Rer1p is no longer able to localize to the Golgi and is transported to the vacuole via the MVB sorting pathway (broken arrows).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198819&req=5

Figure 7: Model of the dynamic function of Rer1p. Rer1p recognizes the signal in the TMD of cargo proteins and actively recycles between the early Golgi and the ER. When it is mislocalized to the late Golgi, it is retrieved to the early Golgi by the COPI vesicles (solid arrows). In COPI mutants, Rer1p is no longer able to localize to the Golgi and is transported to the vacuole via the MVB sorting pathway (broken arrows).
Mentions: The purpose of this study is to demonstrate that Rer1p is a sorting receptor in the cis-Golgi which recognizes signals present in TMDs of a set of ER membrane proteins and retrieves them to the ER (Fig. 7). We have shown the first biochemical evidence for the direct interaction between Rer1p and the TMD of Sec12p (Fig. 1). The following observations support the role of Rer1p as a receptor. First, the TMDs of Sec12p, Sed4p, and Gas1p contain information for the Rer1p-dependent retrieval to the ER, and the spatial locations of polar residues in these TMDs are important for the recognition by Rer1p (Sato et al. 1996; Letourneur and Cosson 1998; Sato, K., and A. Nakano, unpublished data). Second, there is an apparent competition for Rer1p between Sec12p and Sec71p, suggesting a saturable mechanism for the retrieval (Sato et al. 1997). Rer1p is a limiting component in this competition. We have also demonstrated that coatomer plays a critical role for the function and localization of Rer1p. Mfα1p fusions of Sec12p, Sec71p, and Sec63p whose correct ER localization depends on Rer1p are all mislocalized to the trans-Golgi in an α-COP mutant (Sato et al. 1997). Rer1p itself is vigorously recycling between the Golgi and the ER in a COPI-dependent fashion (Fig. 3 and Fig. 6 c) and is mistargeted to the vacuole in α-, β′-, and γ-COP mutants (Fig. 6, a and b). Most importantly, coatomer subunits bind to the COOH-terminal tail of Rer1p in vitro (Fig. 6 e). All of these observations led us to conclude that Rer1p is a novel type of receptor that recognizes a retrieval signal in the lipid bilayer. Such a ligand–receptor interaction in the lipid milieu has been long proposed to explain membrane protein sorting. The binding of Rer1p with the Sec12p TMD would provide an ideal example to study the mode of interaction from a structural viewpoint as well.

Bottom Line: Either a lesion of coatomer or deletion of the COOH-terminal tail of Rer1p causes its mislocalization to the vacuole.The COOH-terminal Rer1p tail interacts in vitro with a coatomer complex containing alpha and gamma subunits.These findings not only give the proof that Rer1p is a novel type of retrieval receptor recognizing the TMD in the Golgi but also indicate that coatomer actively regulates the function and localization of Rer1p.

View Article: PubMed Central - PubMed

Affiliation: Molecular Membrane Biology Laboratory, RIKEN (The Institute of Physical and Chemical Research), Saitama 351-0198, Japan. satoken@postman.riken.go.jp

ABSTRACT
Rer1p, a yeast Golgi membrane protein, is required for the retrieval of a set of endoplasmic reticulum (ER) membrane proteins. We present the first evidence that Rer1p directly interacts with the transmembrane domain (TMD) of Sec12p which contains a retrieval signal. A green fluorescent protein (GFP) fusion of Rer1p rapidly cycles between the Golgi and the ER. Either a lesion of coatomer or deletion of the COOH-terminal tail of Rer1p causes its mislocalization to the vacuole. The COOH-terminal Rer1p tail interacts in vitro with a coatomer complex containing alpha and gamma subunits. These findings not only give the proof that Rer1p is a novel type of retrieval receptor recognizing the TMD in the Golgi but also indicate that coatomer actively regulates the function and localization of Rer1p.

Show MeSH
Related in: MedlinePlus