scholarly journals Quality control in the secretory assembly line

2001 ◽  
Vol 356 (1406) ◽  
pp. 147-150 ◽  
Author(s):  
Ari Helenius
Keyword(s):  
Quality Control ◽  
Control System ◽  
Intracellular Transport ◽  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Assembly Line ◽  
Eukaryotic Cells ◽  
Unfolded Proteins ◽  
Different Types ◽  
Sorting System

As a rule, only proteins that have reached a native, folded and assembled structure are transported to their target organelles and compartments within the cell. In the secretory pathway of eukaryotic cells, this type of sorting is particularly important. A variety of molecular mechanisms are involved that distinguish between folded and unfolded proteins, modulate their intracellular transport, and induce degradation if they fail to fold. This phenomenon, called quality control, occurs at several levels and involves different types of folding sensors. The quality control system provides a stringent and versatile molecular sorting system that guaranties fidelity of protein expression in the secretory pathway.

scholarly journals Activation of Mammalian Unfolded Protein Response Is Compatible with the Quality Control System Operating in the Endoplasmic Reticulum

2004 ◽  
Vol 15 (6) ◽  
pp. 2537-2548 ◽  
Author(s):  
Satomi Nadanaka ◽  
Hiderou Yoshida ◽  
Fumi Kano ◽  
Masayuki Murata ◽  
Kazutoshi Mori
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Control System ◽  
Golgi Apparatus ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Unfolded Proteins ◽  
Unfolded Protein ◽  
Protein Response

Newly synthesized secretory and transmembrane proteins are folded and assembled in the endoplasmic reticulum (ER) where an efficient quality control system operates so that only correctly folded molecules are allowed to move along the secretory pathway. The productive folding process in the ER has been thought to be supported by the unfolded protein response (UPR), which is activated by the accumulation of unfolded proteins in the ER. However, a dilemma has emerged; activation of ATF6, a key regulator of mammalian UPR, requires intracellular transport from the ER to the Golgi apparatus. This suggests that unfolded proteins might be leaked from the ER together with ATF6 in response to ER stress, exhibiting proteotoxicity in the secretory pathway. We show here that ATF6 and correctly folded proteins are transported to the Golgi apparatus via the same route and by the same mechanism under conditions of ER stress, whereas unfolded proteins are retained in the ER. Thus, activation of the UPR is compatible with the quality control in the ER and the ER possesses a remarkable ability to select proteins to be transported in mammalian cells in marked contrast to yeast cells, which actively utilize intracellular traffic to deal with unfolded proteins accumulated in the ER.

scholarly journals Assembly and regulation of γ-tubulin complexes

Open Biology ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 170266 ◽  
Author(s):  
Dorian Farache ◽  
Laurent Emorine ◽  
Laurence Haren ◽  
Andreas Merdes
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Intracellular Transport ◽  
Eukaryotic Cells ◽  
Cellular Structures ◽  
Activator Proteins ◽  
Multiprotein Complexes ◽  
Microtubule Organizing Centres ◽  
Different Types ◽  
Ring Complexes

Microtubules are major constituents of the cytoskeleton in all eukaryotic cells. They are essential for chromosome segregation during cell division, for directional intracellular transport and for building specialized cellular structures such as cilia or flagella. Their assembly has to be controlled spatially and temporally. For this, the cell uses multiprotein complexes containing γ-tubulin. γ-Tubulin has been found in two different types of complexes, γ-tubulin small complexes and γ-tubulin ring complexes. Binding to adaptors and activator proteins transforms these complexes into structural templates that drive the nucleation of new microtubules in a highly controlled manner. This review discusses recent advances on the mechanisms of assembly, recruitment and activation of γ-tubulin complexes at microtubule-organizing centres.

scholarly journals DNA Damaged Induced Cell Death in Oocytes

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5714
Author(s):  
Jakob Gebel ◽  
Marcel Tuppi ◽  
Nicole Sänger ◽  
Björn Schumacher ◽  
Volker Dötsch
Keyword(s):  
Quality Control ◽  
Control System ◽  
Molecular Mechanisms ◽  
P53 Protein ◽  
Genetic Material ◽  
Fruit Fly ◽  
Quality Control System ◽  
Premature Menopause ◽  
Dna Double Strand Breaks ◽  
Homologous Chromosomes

The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.

scholarly journals The yeast p24 complex regulates GPI-anchored protein transport and quality control by monitoring anchor remodeling

2011 ◽  
Vol 22 (16) ◽  
pp. 2924-2936 ◽  
Author(s):  
Guillaume A. Castillon ◽  
Auxiliadora Aguilera-Romero ◽  
Javier Manzano-Lopez ◽  
Sharon Epstein ◽  
Kentaro Kajiwara ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Intracellular Transport ◽  
Protein Transport ◽  
Eukaryotic Cells ◽  
Secretory Proteins ◽  
Dependent Manner ◽  
Gpi Anchor ◽  
The Status

Glycosylphosphatidylinositol (GPI)-anchored proteins are secretory proteins that are attached to the cell surface of eukaryotic cells by a glycolipid moiety. Once GPI anchoring has occurred in the lumen of the endoplasmic reticulum (ER), the structure of the lipid part on the GPI anchor undergoes a remodeling process prior to ER exit. In this study, we provide evidence suggesting that the yeast p24 complex, through binding specifically to GPI-anchored proteins in an anchor-dependent manner, plays a dual role in their selective trafficking. First, the p24 complex promotes efficient ER exit of remodeled GPI-anchored proteins after concentration by connecting them with the COPII coat and thus facilitates their incorporation into vesicles. Second, it retrieves escaped, unremodeled GPI-anchored proteins from the Golgi to the ER in COPI vesicles. Therefore the p24 complex, by sensing the status of the GPI anchor, regulates GPI-anchored protein intracellular transport and coordinates this with correct anchor remodeling.

Direct evidence of cytosolic PNGase activity in Arabidopsis thaliana: in vitro assay system for plant cPNGase activity

2021 ◽  
Author(s):  
Sahoko Shirai ◽  
Ryota Uemura ◽  
Megumi Maeda ◽  
Hiroyuki Kajiura ◽  
Ryo Misaki ◽  
...  
Keyword(s):  
Quality Control ◽  
Arabidopsis Thaliana ◽  
Control System ◽  
Direct Evidence ◽  
Protein Quality ◽  
In Vitro Assay ◽  
Eukaryotic Cells ◽  
Vitro Assay ◽  
Protein Quality Control System

Abstract Cytosolic peptide: N-glycanase (cPNGase), which occurs ubiquitously in eukaryotic cells, is involved in the de-N-glycosylation of misfolded glycoproteins in the protein quality control system. In this study, we aimed to provide direct evidence of plant cPNGase activity against a denatured glycoprotein using a crude extract prepared from a mutant line of Arabidopsis thaliana lacking two acidic PNGase genes.

scholarly journals An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism.

1996 ◽  
Vol 133 (3) ◽  
pp. 517-527 ◽  
Author(s):  
P S Kim ◽  
O Y Kwon ◽  
P Arvan
Keyword(s):  
Quality Control ◽  
Cell Biology ◽  
Intracellular Transport ◽  
Secretory Pathway ◽  
Storage Disease ◽  
Thyroid Tissue ◽  
Temperature Sensitive ◽  
Control Mechanisms ◽  
Er Quality Control ◽  
Hormone Synthesis

In humans, deficient thyroglobulin (Tg, the thyroid prohormone) is an important cause of congenital hypothyroid goiter; further, homozygous mice expressing two cog/cog alleles (linked to the Tg locus) exhibit the same phenotype. Tg mutations might affect multiple different steps in thyroid hormone synthesis; however, the microscopic and biochemical phenotype tends to involve enlargement of the thyroid ER and accumulation of protein bands of M(r) < 100. To explore further the cell biology of this autosomal recessive illness, we have examined the folding and intracellular transport of newly synthesized Tg in cog/cog thyroid tissue. We find that mutant mice synthesize a full-length Tg, which appears to undergo normal N-linked glycosylation and glucose trimming. Nevertheless, in the mutant, Tg is deficient in the folding that leads to homodimerization, and there is a deficiency in the quantity of intracellular Tg transported to the distal portion of the secretory pathway. Indeed, we find that the underlying disorder in cog/cog mice is a thyroid ER storage disease, in which a temperature-sensitive Tg folding defect, in conjunction with normal ER quality control mechanisms, leads to defective Tg export. In relation to quality control, we find that the physiological response in this illness includes the specific induction of five molecular chaperones in the thyroid ER. Based on the pattern of chaperone binding, different potential roles for individual chaperones are suggested in glycoprotein folding, retention, and degradation in this ER storage disease.

scholarly journals Protein folding state-dependent sorting at the Golgi apparatus

2019 ◽  
Vol 30 (17) ◽  
pp. 2296-2308 ◽  
Author(s):  
Doris Hellerschmied ◽  
Yevgeniy V. Serebrenik ◽  
Lin Shao ◽  
George M. Burslem ◽  
Craig M. Crews
Keyword(s):  
Quality Control ◽  
Golgi Apparatus ◽  
Protein Unfolding ◽  
Secretory Pathway ◽  
Protein Quality ◽  
Specific Protein ◽  
Major Protein ◽  
Unfolded Proteins ◽  
Lysosomal Degradation ◽  
Folded Proteins

In eukaryotic cells, organelle-specific protein quality control (PQC) is critical for maintaining cellular homeostasis. Despite the Golgi apparatus being the major protein processing and sorting site within the secretory pathway, how it contributes to PQC has remained largely unknown. Using different chemical biology-based protein unfolding systems, we reveal the segregation of unfolded proteins from folded proteins in the Golgi. Quality control (QC) substrates are subsequently exported in distinct carriers, which likely contain unfolded proteins as well as highly oligomerized cargo that mimic protein aggregates. At an additional sorting step, oligomerized proteins are committed to lysosomal degradation, while unfolded proteins localize to the endoplasmic reticulum (ER) and associate with chaperones. These results highlight the existence of checkpoints at which QC substrates are selected for Golgi export and lysosomal degradation. Our data also suggest that the steady-state ER localization of misfolded proteins, observed for several disease-causing mutants, may have different origins.

scholarly journals Saccharomyces cerevisiae, a model to study sterol uptake and transport in eukaryotes

2005 ◽  
Vol 33 (5) ◽  
pp. 1186-1188 ◽  
Author(s):  
S. Reiner ◽  
D. Micolod ◽  
R. Schneiter
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Intracellular Transport ◽  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Eukaryotic Cells ◽  
Lipid Uptake ◽  
Anaerobic Conditions ◽  
Transport Pathway ◽  
Uptake And Transport ◽  
Mutant Collection

The molecular mechanisms that govern intracellular transport of sterols in eukaryotic cells are only poorly understood. Saccharomyces cerevisiae is a facultative anaerobic organism that requires supplementation with unsaturated fatty acids and sterols to grow in the absence of oxygen, as the synthesis of these lipids requires molecular oxygen. The fact that yeast grows well under anaerobic conditions indicates that lipid uptake is rapid and efficient. To identify components in this lipid uptake and transport pathway, we screened the yeast mutant collection for genes that are essential under anaerobic conditions. Out of the approx. 4800 non-essential genes represented in the mutant collection, 37 were required for growth under anaerobic conditions. Uptake assays using radiolabelled cholesterol revealed that 16 of these genes are required for cholesterol uptake/transport and esterification. Further characterization of the precise role of these genes is likely to advance our understanding of this elusive pathway in yeast and may prove to be relevant to understand sterol homoeostasis in higher eukaryotic cells.

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