Journal ArticleDOI
Protein Folding and Modification in the Mammalian Endoplasmic Reticulum
Ineke Braakman,Neil J. Bulleid +1 more
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Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation.Abstract:
Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation. The path taken by a polypeptide through the secretory pathway starts with its translocation across or into the ER membrane. It then must fold and be modified correctly in the ER before being transported via the Golgi apparatus to the cell surface or another destination. Being physically segregated from the cytosol means that the ER lumen has a distinct folding environment. It contains much of the machinery for fulfilling the task of protein production, including complex pathways for folding, assembly, modification, quality control, and recycling. Importantly, the compartmentalization means that several modifications that do not occur in the cytosol, such as glycosylation and extensive disulfide bond formation, can occur to secreted proteins to enhance their stability before their exposure to the extracellular milieu. How these various machineries interact during the normal pathway of folding and protein secretion is the subject of this review.read more
Citations
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Journal ArticleDOI
Molecular Chaperone Functions in Protein Folding and Proteostasis
TL;DR: This review focuses on recent advances in understanding the mechanisms of chaperone action in promoting and regulating protein folding and on the pathological consequences of protein misfolding and aggregation.
Journal ArticleDOI
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Claudio Hetz,Bertrand Mollereau +1 more
TL;DR: An overview of the most recent findings addressing the biological relevance of ER stress in the nervous system is provided.
Journal ArticleDOI
Endoplasmic Reticulum Stress and Associated ROS
TL;DR: Persistent ER stress and protein misfolding-initiated ROS cascades and their significant roles in the pathogenesis of multiple human disorders, including neurodegenerative diseases, diabetes mellitus, atherosclerosis, inflammation, ischemia, and kidney and liver diseases are reviewed.
Journal ArticleDOI
Autophagy-Independent Functions of the Autophagy Machinery
TL;DR: Emerging data on the non-autophagic functions of autophagy-relevant proteins is discussed and it is suggested that most, if not all, components of the molecular machinery for Autophagy also mediate autophagic-independent functions.
Journal ArticleDOI
Endoplasmic Reticulum Stress signalling - from basic mechanisms to clinical applications
Aitor Almanza,Antonio Carlesso,Chetan Chintha,Stuart Creedican,Dimitrios Doultsinos,Brian Leuzzi,Andreia Luís,Nicole McCarthy,Luigi Montibeller,Sanket More,Alexandra Papaioannou,Franziska Püschel,Maria Livia Sassano,Josip Skoko,Patrizia Agostinis,Jackie de Belleroche,Leif A. Eriksson,Simone Fulda,Adrienne M. Gorman,Sandra Healy,Andrey V. Kozlov,Cristina Muñoz-Pinedo,Markus Rehm,Eric Chevet,Afshin Samali +24 more
TL;DR: This review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology.
References
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Journal ArticleDOI
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.
Journal ArticleDOI
Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
TL;DR: A ribosomesome-profiling strategy based on the deep sequencing of ribosome-protected mRNA fragments is presented and enables genome-wide investigation of translation with subcodon resolution and is used to monitor translation in budding yeast under both rich and starvation conditions.
Journal ArticleDOI
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
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Journal ArticleDOI
The mammalian unfolded protein response
TL;DR: In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure as mentioned in this paper.
Journal ArticleDOI
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty,Jung Mi Oh,In-Wha Kim,Zuben E. Sauna,Anna Maria Calcagno,Suresh V. Ambudkar,Michael M. Gottesman +6 more
TL;DR: It is hypothesized that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.
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