Sorting things out through endoplasmic reticulum quality control

Tamura, Taku; Sunryd, Johan C.; Hebert, Daniel N.

doi:10.3109/09687688.2010.495354

Cited by 19 publications

(12 citation statements)

References 136 publications

(226 reference statements)

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“…Recently, it has been reported that EDEM1, OS-9 and XTP3-B (and their yeast orthologs; Hanna et al [2012]) may use their ML or MRH domains to associate with oligosaccharides displayed by the type I membrane protein SEL1L, a component of the dislocation machinery containing the E3 ubiquitin ligase HRD1 (Christianson et al, 2012;Christianson et al, 2008;Cormier et al, 2009;Satoh et al, 2010). This led to challenge the ''mannose timer model'' of protein quality control and to propose an alternative ''docking model'' of protein quality control in which oligosaccharides may serve as docking sites for EDEM1 and OS-9 at the SEL1L/HRD1 dislocon, rather than as signal tagging misfolded polypeptides for destruction (Aebi et al, 2010;Tamura et al, 2010). In this work, we have evaluated the consequences and the biological relevance of the oligosaccharide-based association between EDEM1 or OS-9 and SEL1L.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Role of the SEL1L:LC3-I Complex as an ERAD Tuning Receptor in the Mammalian ER

Bernasconi¹,

Galli²,

Noack³

et al. 2012

Molecular Cell

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Several regulators of endoplasmic reticulum (ER)-associated degradation (ERAD) have a shorter half-life compared to conventional ER chaperones. At steady state, they are selectively removed from the ER by poorly defined events collectively referred to as ERAD tuning. Here we identify the complex comprising the type-I transmembrane protein SEL1L and the cytosolic protein LC3-I as an ERAD tuning receptor regulating the COPII-independent, vesicle-mediated removal of the lumenal ERAD regulators EDEM1 and OS-9 from the ER. Expression of folding-defective polypeptides enhances the lumenal content of EDEM1 and OS-9 by inhibiting their SEL1L:LC3-I-mediated segregation. This raises ERAD activity in the absence of UPR-induction. The mouse hepatitis virus (MHV) subverts ERAD tuning for replication. Consistently, SEL1L or LC3 silencing impair the MHV life cycle. Collectively, our data provide new molecular information about the ERAD tuning mechanisms that regulate ERAD in mammalian cells at the post translational level and how these mechanisms are hijacked by a pathogen.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Role of the SEL1L:LC3-I Complex as an ERAD Tuning Receptor in the Mammalian ER

Bernasconi¹,

Galli²,

Noack³

et al. 2012

Molecular Cell

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“…Retention in the subcellular compart ments is an indication of protein misfold ing, often leading to degradation (37). This observation prompted us to quan tify the cellular expression levels of the different pendrin protein variants, on the basis of the hypothesis that abundance of variants with significant retention in the ER should be reduced with respect to variants with targeting to the PM.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants

Moraes

Bernardinelli

Zocal

et al. 2016

Mol Med

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“…The quality control machinery of the secretory pathway recognizes misfolded proteins and targets them for degradation (17). To be sure that domain 2 was properly folded, we tested its oligomeric state by gel filtration chromatography.…”

Section: Figurementioning

confidence: 99%

Niemann–Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding

Deffieu

Pfeffer²

2011

Proc. Natl. Acad. Sci. U.S.A.

149

173

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Niemann-Pick type C1 (NPC1) protein is needed for cellular utilization of low-density lipoprotein-derived cholesterol that has been delivered to lysosomes. The protein has 13 transmembrane domains, three large lumenal domains, and a cytoplasmic tail. NPC1's lumenally oriented, N-terminal domain binds cholesterol and has been proposed to receive cholesterol from NPC2 protein as part of the process by which cholesterol is exported from lysosomes into the cytosol. Using surface plasmon resonance and affinity chromatography, we show here that the second lumenal domain of NPC1 binds directly to NPC2 protein. For these experiments, a soluble NPC1 lumenal domain 2 was engineered by replacing adjacent transmembrane domains with antiparallel coiled-coil sequences. Interaction of NPC2 with NPC1 lumenal domain 2 is only detected at acidic pH, conditions that are optimal for cholesterol binding to NPC2 and transfer to NPC1; the pH is also appropriate for the acidic environment where binding would take place. Binding to NPC1 domain 2 requires the presence of cholesterol on NPC2 protein, a finding that supports directional transfer of cholesterol from NPC2 onto NPC1's N-terminal domain. Finally, human disease-causing mutations in NPC1 domain 2 decrease NPC2 binding, suggesting that NPC2 binding is necessary for NPC1 function in humans. These data support a model in which NPC1 domain 2 holds NPC2 in position to facilitate directional cholesterol transfer from NPC2 onto NPC1 protein for export from lysosomes.cholesterol trafficking | Niemann-Pick type C disease A major source of cellular cholesterol is endocytosed as lowdensity lipoprotein, which is delivered to late endosomes and lysosomes where cholesterol is released (1). Within late endosomes and lysosomes, Niemann-Pick type C1 (NPC1) and NPC2 proteins are required for the subsequent delivery of cholesterol to other intracellular compartments (2). NPC1 is a large, 1,254 residue, integral membrane protein that is predicted to span the bilayer 13 times (3, 4); it contains a lumenally oriented, N-terminal cholesterol binding site that interacts with the 3β-hydroxyl end of the cholesterol molecule (5-7). NPC2 is a much smaller, soluble lysosomal protein of 132 amino acid residues (8) that binds cholesterol in an opposite orientation via cholesterol's isooctyl side chain (9-11). The importance of NPC1 and NPC2 for cholesterol and glycosphingolipid homeostasis is demonstrated in Niemann-Pick type C disease: patients carrying homozygous mutations in either of these proteins suffer neurodegeneration and die in childhood due to cholesterol and glycosphingolipid accumulation in the brain, liver, and lungs (12, 13).NPC2 is thought to play an important role in extracting cholesterol from intralysosomal membranes that are rich in cholesterol and bis(monoacylglycerol) phosphate. Transfer of that cholesterol to NPC1 is proposed to facilitate passage of this hydrophobic sterol across the glycocalyx that lines the inner lysosomal membrane.Recent studies using purified NPC2 and a soluble con...

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Sorting things out through endoplasmic reticulum quality control

Cited by 19 publications

References 136 publications

RETRACTED: Role of the SEL1L:LC3-I Complex as an ERAD Tuning Receptor in the Mammalian ER

RETRACTED: Role of the SEL1L:LC3-I Complex as an ERAD Tuning Receptor in the Mammalian ER

Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants

Niemann–Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding

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