scholarly journals How to Avoid a No-Deal ER Exit

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1051 ◽  
Author(s):  
Tiziana Anelli ◽  
Paola Panina-Bordignon
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Protein Concentration ◽  
Secretory Proteins ◽  
Protein Accumulation ◽  
Secreted Protein ◽  
Native Structure ◽  
Golgi Compartment ◽  
Abnormal Increase ◽  
Er Exit Sites

Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation. After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes. Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments. Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation. Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes. Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER. In both cases, diseases can arise. In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.

scholarly journals Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

2014 ◽  
Vol 206 (6) ◽  
pp. 751-762 ◽  
Author(s):  
Kota Saito ◽  
Koh Yamashiro ◽  
Noriko Shimazu ◽  
Tomoya Tanabe ◽  
Kenji Kontani ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Secretory Proteins ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Transport Vesicles ◽  
Nucleotide Exchange Factor ◽  
Receptor Component ◽  
Er Exit Sites ◽  
Guanosine Triphosphatase ◽  
Trimeric Structure

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60–90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate–bound Sar1 generated by Sec12 localized at ER exit sites.

scholarly journals Proteasome and thiol involvement in quality control of glycosylphosphatidylinositol anchor addition

1998 ◽  
Vol 332 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Barry WILBOURN ◽  
Darren N. NESBETH ◽  
Linda J. WAINWRIGHT ◽  
Mark C. FIELD
Keyword(s):  
Quality Control ◽  
Cysteine Residue ◽  
Retention Mechanism ◽  
Secretory Proteins ◽  
Aggregate Formation ◽  
Er Quality Control ◽  
Additional Information ◽  
Intracellular Degradation ◽  
Processing Signal ◽  
Ubiquitination System

Improperly processed secretory proteins are degraded by a hydrolytic system that is associated with the endoplasmic reticulum (ER) and appears to involve re-export of lumenal proteins into the cytoplasm for ultimate degradation by the proteasome. The chimaeric protein hGHDAF28, which contains a crippled glycosylphosphatidylinositol (GPI) C-terminal signal peptide, is degraded by a pathway highly similar to that for other ER-retained proteins and is characterized by formation of disulphide-linked aggregates, failure to reach the Golgi complex and intracellular degradation with a half life of ∼ 2 h. Here we show that N-acetyl-leucinal-leucinal-norleucinal, MG-132 and lactacystin, all inhibitors of the proteasome, protect hGHDAF28; hGHDAF28 is still proteolytically cleaved in the presence of lactacystin or MG-132, by the removal of ∼ 2 kDa, but the truncated fragment is not processed further. We demonstrate that the ubiquitination system accelerates ER-degradation of hGHDAF28, but is not essential to the process. Overall, these findings indicate that GPI quality control is mediated by the cytoplasmic proteasome. We also show that the presence of a cysteine residue in the GPI signal of hGHDAF28 is required for retention and degradation, as mutation of this residue to serine results in secretion of the fusion protein, implicating thiol-mediated retention as a mechanism for quality control of some GPI signals. Removal of the cysteine also prevents inclusion of hGHDAF28 in disulphide-linked aggregates, indicating that aggregate formation is an additional retention mechanism for this class of protein. Therefore our data suggest that an unpaired terminal cysteine is the retention motif of the hGHDAF28 GPI-processing signal and that additional information may be required for efficient engagement of ER quality control systems by the majority of GPI signals which lack cysteine residues.

scholarly journals Limited ER quality control for GPI-anchored proteins

2016 ◽  
Vol 213 (6) ◽  
pp. 693-704 ◽  
Author(s):  
Natalia Sikorska ◽  
Leticia Lemus ◽  
Auxiliadora Aguilera-Romero ◽  
Javier Manzano-Lopez ◽  
Howard Riezman ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Misfolded Proteins ◽  
Control Mechanisms ◽  
Gpi Anchor ◽  
Er Quality Control ◽  
Entire Class ◽  
Er Export ◽  
Export Signal

Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant.

Glycosylation-directed quality control of protein folding

2015 ◽  
Vol 16 (12) ◽  
pp. 742-752 ◽  
Author(s):  
Chengchao Xu ◽  
Davis T. W. Ng
Keyword(s):  
Quality Control ◽  
Protein Folding

scholarly journals The GTPase Nog1 co-ordinates the assembly, maturation and quality control of distant ribosomal functional centers

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Purnima Klingauf-Nerurkar ◽  
Ludovic C Gillet ◽  
Daniela Portugal-Calisto ◽  
Michaela Oborská-Oplová ◽  
Martin Jäger ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Atpase Activity ◽  
Ribosomal Protein ◽  
Peptidyl Transferase ◽  
Peptidyl Transferase Center ◽  
Eukaryotic Ribosome ◽  
Ribosomal Stalk ◽  
Exit Tunnel ◽  
Ribosome Formation

Eukaryotic ribosome precursors acquire translation competence in the cytoplasm through stepwise release of bound assembly factors, and proofreading of their functional centers. In case of the pre-60S, these steps include removal of placeholders Rlp24, Arx1 and Mrt4 that prevent premature loading of the ribosomal protein eL24, the protein-folding machinery at the polypeptide exit tunnel (PET), and the ribosomal stalk, respectively. Here, we reveal that sequential ATPase and GTPase activities license release factors Rei1 and Yvh1 to trigger Arx1 and Mrt4 removal. Drg1-ATPase activity removes Rlp24 from the GTPase Nog1 on the pre-60S; consequently, the C-terminal tail of Nog1 is extracted from the PET. These events enable Rei1 to probe PET integrity and catalyze Arx1 release. Concomitantly, Nog1 eviction from the pre-60S permits peptidyl transferase center maturation, and allows Yvh1 to mediate Mrt4 release for stalk assembly. Thus, Nog1 co-ordinates the assembly, maturation and quality control of distant functional centers during ribosome formation.

Forage productivity of smooth brome grass mixtures under the application of growth regulators

2021 ◽  
pp. 9-15
Author(s):  
В.Г. Васин ◽  
М.С. Кригер ◽  
С.А. Васин
Keyword(s):  
Growth Regulators ◽  
Crop Production ◽  
Protein Concentration ◽  
Matter Content ◽  
Energy Yield ◽  
Protein Accumulation ◽  
Dry Matter Content ◽  
Smooth Brome ◽  
Arable Farming ◽  
Brome Grass

Исследования проведены в 2019–2020 годах в экспериментальном севообороте научно-исследовательской лаборатории «Корма» кафедры «Растениеводство и земледелие» Самарского ГАУ. В статье представлены данные по кормовой продуктивности травосмесей костреца безостого с кострецом прямым, бобовыми травами и черноголовником многобрачным при применении стимуляторов «Матрица роста» и «Гуми-20М». В состав исследуемых травосмесей входили эспарцет песчаный, люцерна посевная и лядвенец рогатый. Посев проведён в мае 2015 года. Исследование охватывало фазу вымётывания костреца безостого и прямого и цветения бобовых, во время которой оценивалась урожайность, определялся химический состав травостоев (особое внимание уделялось содержанию протеина и динамике его изменения), а также проводился учёт кормовых достоинств (накопления сухого вещества, переваримого протеина и выхода обменной энергии). Высокую продуктивность формировали трёх- и четырёхкомпонентные травостои с эспарцетом песчаным и люцерной посевной. Травостои с лядвенцем рогатым обеспечивали максимальные показатели. Наблюдалось отчётливое увеличение всех изучаемых показателей при добавлении бобового компонента. Продуктивность обработанных стимуляторами травосмесей была, как правило, больше, чем в контрольном варианте. Минимальную продуктивность формировали смеси, в которых присутствовали только злаковые компоненты и которые не обрабатывались стимуляторами роста. Также выявлено, что содержание протеина в травостоях с бобовым компонентом было выше, чем в травостоях с мятликовыми культурами, обработка посевов стимуляторами способствовала повышению протеина. Анализ доли компонентов в травостоях показал, что злаковый компонент преобладал над бобовым, однако в некоторых вариантах наблюдалось преобладание эспарцета и люцерны над злаками. Наименьшую долю в травостое составляли лядвенец рогатый и черноголовник многобрачный. Зависимости процентного соотношения компонентов от варианта обработки выявлено не было. The investigation took place at the laboratory “Korma“ of the Samara State Agrarian University (the department of Crop Production and Arable farming) in 2019–2020. The article reports on the productivity of grass mixtures of smooth brome with erect brome, legumes and fodder burnet under the application of growth regulators “Matritsa rosta“ and “Gumi-20M“. The mixtures also contained hungarian sainfoin, alfalfa and birdʼs-foot trefoil. Crops were planted in May 2015. Crops were tested at the heading or flowering stages. The following traits were analyzed: productivity, chemical composition, dry matter content, crude protein and exchange energy yield. The dynamics of protein accumulation was studied. Three- and four-component grass mixtures with hungarian sainfoin and alfalfa showed the highest productivity. Mixtures with birdʼs-foot trefoil performed the best. Introduction of legumes into swards positively affected all the traits studied. Generally, the application of growth regulators resulted in higher productivity. Gramineous mixtures had the lowest productivity under no treatment. Swards with legumes provided more protein. The treatment with growth regulators increased protein concentration. Gramineous dominated legumes, however, in some variants hungarian sainfoin and alfalfa were predominant. Birdʼs-foot trefoil and fodder burnet had the smallest share in swords. There was no significant correlation between mixture composition and treatments.

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