Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles

Otte, Stefan; Barlowe, Charles

doi:10.1038/ncb1195

Cited by 102 publications

(99 citation statements)

References 29 publications

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“…Erv29p, the yeast orthologue of Surf4, acts as a cargo receptor for glycosylated ␣-factor in yeast (Belden and Barlowe, 2001;Otte and Barlowe, 2004). Although a knockdown of Surf4 had no effect on total protein secretion, it remains possible that human Surf4 also operates as a cargo receptor for a limited set of proteins that would not be apparent in a global secretion assay.…”

Section: Discussionmentioning

confidence: 96%

“…Maturation of carboxypeptidase Y and proteinase A, but not other secretory proteins such as invertase, also depends on Erv29p (Caldwell et al, 2001). In support of the cargo receptor concept, a hydrophobic sorting signal was identified in ␣-factor that is required for its interaction with Erv29p and efficient transport (Belden and Barlowe, 2001;Otte and Barlowe, 2004). Erv29p is conserved among eukaryotes and the mammalian orthologue has been designated Surf4 (Reeves and Fried, 1995).…”

Section: Introductionmentioning

confidence: 93%

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The Cargo Receptors Surf4, Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC)-53, and p25 Are Required to Maintain the Architecture of ERGIC and Golgi

Mitrović

Ben-Tekaya

Koegler

et al. 2008

MBoC

115

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Rapidly cycling proteins of the early secretory pathway can operate as cargo receptors. Known cargo receptors are abundant proteins, but it remains mysterious why their inactivation leads to rather limited secretion phenotypes. Studies of Surf4, the human orthologue of the yeast cargo receptor Erv29p, now reveal a novel function of cargo receptors. Surf4 was found to interact with endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-53 and p24 proteins. Silencing Surf4 together with ERGIC-53 or silencing the p24 family member p25 induced an identical phenotype characterized by a reduced number of ERGIC clusters and fragmentation of the Golgi apparatus without effect on anterograde transport. Live imaging showed decreased stability of ERGIC clusters after knockdown of p25. Silencing of Surf4/ERGIC-53 or p25 resulted in partial redistribution of coat protein (COP) I but not Golgi matrix proteins to the cytosol and partial resistance of the cis-Golgi to brefeldin A. These findings imply that cargo receptors are essential for maintaining the architecture of ERGIC and Golgi by controlling COP I recruitment. INTRODUCTIONThe secretory pathway of higher eukaryotic cells is composed of the three membrane organelles endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), and Golgi (Bonifacino and Glick, 2004;Appenzeller-Herzog and Hauri, 2006). Maintenance of these organelles requires a balance of anterograde (secretory) and retrograde vesicular traffic. Anterograde traffic from ER to ERGIC is mediated by coat protein (COP) II vesicles that form at ER exit sites (Aridor et al., 1995;Zeuschner et al., 2006) and fuse with the ERGIC that consists of a few hundred tubulovesicular membrane clusters in vicinity of ER exit sites (AppenzellerHerzog and Hauri, 2006). Transport from ERGIC to Golgi is mediated by pleomorphic vesicles (Ben-Tekaya et al., 2005) that carry COP I (Presley et al., 1997;Scales et al., 1997), although the mechanism of their formation remains unknown. Retrograde traffic mediated by COP I vesicles can occur from ERGIC or Golgi and recycles membrane proteins that possess either dilysine signals, including ERGIC-53 and KDEL-receptor, or diphenylalanine signals, such as members of the 24 protein family. This rapid COP I-dependent recycling is distinct from the slow Golgi-to-ER recycling of Golgi resident proteins that is COP I independent and can be either constitutive or induced (Storrie, 2005).Major constituents of anterograde and retrograde transport vesicles are transmembrane cargo receptors that mediate protein sorting by linking soluble cargo on the luminal side and coat assembly on the cytoplasmic side. To date, only few cargo receptors have been studied in detail. The polytopic transmembrane protein Erv29p is known to cycle between ER and Golgi in yeast and to operate as a cargo receptor (Belden and Barlowe, 2001). Erv29p is required for efficient packaging of the glycosylated ␣-factor pheromone precursor into COP II vesicles departing from the ER. Maturation of carboxypeptidase Y...

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 93%

The Cargo Receptors Surf4, Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC)-53, and p25 Are Required to Maintain the Architecture of ERGIC and Golgi

Mitrović

Ben-Tekaya

Koegler

et al. 2008

MBoC

115

View full text Add to dashboard Cite

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“…For example, certain soluble cargo proteins are incorporated into transport vesicles in a manner dependent on cargo receptors. Cargo receptors are transmembrane proteins that can interact with both cargo and coat proteins and bridge their interaction during the formation of the transport vesicles (14). A well documented example is the KDEL receptor, which is responsible for the Golgi-to-ER retrieval of soluble ER-resident proteins bearing a KDEL retention signal (15,16).…”

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confidence: 99%

Isoform-selective Oligomer Formation of Saccharomyces cerevisiae p24 Family Proteins

Hirata

Nihei

Nakano

2013

Journal of Biological Chemistry

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Background: p24 family proteins function as cargo receptors for ER-Golgi transport. Results: Genetic and physical interactions among eight known and one newly identified S. cerevisiae p24 proteins were determined. Conclusion: Yeast p24 proteins function in several functionally redundant complexes, including one containing a novel p24 isoform induced under respiratory conditions. Significance: This is the first comprehensive study of the yeast p24 complexes.

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“…The only previously characterized function of the α-factor pro region is to interact with the ER export receptor Erv29 [24]. We therefore hypothesized that Erv29-dependent acceleration of ER export was responsible for the ability of the pro region to enhance secretion of msGFP.…”

Section: Resultsmentioning

confidence: 99%

Secretion of a foreign protein from budding yeasts is enhanced by cotranslational translocation and by suppression of vacuolar targeting

Fitzgerald

Glick

2014

Microb Cell Fact

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Background: Budding yeasts are often used to secrete foreign proteins, but the efficiency is variable. To identify roadblocks in the yeast secretory pathway, we used a monomeric superfolder GFP (msGFP) as a visual tracer in Saccharomyces cerevisiae and Pichia pastoris. Results: One roadblock for msGFP secretion is translocation into the ER. Foreign proteins are typically fused to the bipartite α-factor secretion signal, which consists of the signal sequence followed by the pro region. The α-factor signal sequence directs posttranslational translocation. For msGFP, posttranslational translocation is inefficient with the α-factor signal sequence alone but is stimulated by the pro region. This requirement for the pro region can be bypassed by using the Ost1 signal sequence, which has been shown to direct cotranslational translocation. A hybrid secretion signal consisting of the Ost1 signal sequence followed by the α-factor pro region drives efficient translocation followed by rapid ER export. A second roadblock for msGFP secretion in S. cerevisiae occurs during exit from the Golgi, when some of the msGFP molecules are diverted to the vacuole. Deletion of the sorting receptor Vps10 prevents vacuolar targeting of msGFP at the expense of missorting vacuolar hydrolases such as carboxypeptidase Y (CPY) to the culture medium. However, a truncation of Vps10 blocks vacuolar targeting of msGFP while permitting CPY to be sorted normally. Conclusions: With budding yeasts, if the secretion or processing of a foreign protein is poor, we recommend two options. First, use the Ost1 signal sequence to achieve efficient entry into the secretory pathway while avoiding the processing issues associated with the α-factor pro region. Second, truncate Vps10 to suppress diversion to the vacuole. These insights obtained with msGFP highlight the value of applying cell biological methods to study yeast secretion.

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Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles

Cited by 102 publications

References 29 publications

The Cargo Receptors Surf4, Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC)-53, and p25 Are Required to Maintain the Architecture of ERGIC and Golgi

The Cargo Receptors Surf4, Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC)-53, and p25 Are Required to Maintain the Architecture of ERGIC and Golgi

Isoform-selective Oligomer Formation of Saccharomyces cerevisiae p24 Family Proteins

Secretion of a foreign protein from budding yeasts is enhanced by cotranslational translocation and by suppression of vacuolar targeting

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