scholarly journals Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl‐tRNA synthetase activity

FEBS Journal ◽  
2018 ◽  
Vol 285 (14) ◽  
pp. 2654-2661 ◽  
Author(s):  
Martine Comisso ◽  
Alice Hadchouel ◽  
Jacques Blic ◽  
Marc Mirande
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Trna Synthetase ◽  
Synthetase Activity ◽  
Alveolar Proteinosis ◽  
Methionyl Trna Synthetase

scholarly journals Methionyl-tRNA synthetase novel mutation causes pulmonary alveolar proteinosis

2019 ◽  
Vol 40 (2) ◽  
pp. 195-198 ◽  
Author(s):  
Mohammed Alzaid ◽  
Abdullah Alshamrani ◽  
Adel Al Harbi ◽  
Ayed Alenzi ◽  
Sarar Mohamed
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Novel Mutation ◽  
Trna Synthetase ◽  
Alveolar Proteinosis ◽  
Methionyl Trna Synthetase

scholarly journals Biallelic Mutations of Methionyl-tRNA Synthetase Cause a Specific Type of Pulmonary Alveolar Proteinosis Prevalent on Réunion Island

2015 ◽  
Vol 96 (5) ◽  
pp. 826-831 ◽  
Author(s):  
Alice Hadchouel ◽  
Thomas Wieland ◽  
Matthias Griese ◽  
Enrico Baruffini ◽  
Bettina Lorenz-Depiereux ◽  
...  
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Trna Synthetase ◽  
Reunion Island ◽  
Réunion Island ◽  
Alveolar Proteinosis ◽  
Biallelic Mutations ◽  
Methionyl Trna Synthetase

scholarly journals Association of methionyl-tRNA synthetase with detergent-insoluble components of the rough endoplasmic reticulum.

1983 ◽  
Vol 96 (4) ◽  
pp. 1138-1147 ◽  
Author(s):  
C V Dang ◽  
D C Yang ◽  
T D Pollard
Keyword(s):  
Endoplasmic Reticulum ◽  
Fluorescent Antibody ◽  
Insoluble Fraction ◽  
Trna Synthetase ◽  
Insoluble Residue ◽  
Synthetase Activity ◽  
Fluorochrome Staining ◽  
Antibody Staining ◽  
Triton X ◽  
Methionyl Trna Synthetase

Using fluorescent antibody staining, we have established the association of methionyl-tRNA synthetase with the endoplasmic reticulum in PtK2 cells. After Triton X-100 extraction, 70% of the recovered aminoacyl-tRNA synthetase activity was found in the detergent-insoluble fraction. This fraction of the enzyme remained localized with insoluble endoplasmic reticulum antigens and with ribosomes, which were stained with acridine orange. By both fluorescence microscopy and electron microscopy the organization of the detergent-insoluble residue was found to depend on the composition of the extracting solution. After extraction with a microtubule-stabilizing buffer containing EGTA, Triton X-100, and polyethylene glycol (Osburn, M., and K. Weber, 1977, Cell, 12:561-571) the ribosomes were aggregated in large clusters with remnants of membranes. After extraction with a buffer containing Triton X-100, sucrose, and CaCl2 (Fulton, A. B., K. M. Wang, and S. Penman, 1980, Cell, 20:849-857), the ribosomes were in small clusters and there were few morphologically recognizable membranes. In both cases the methionyl-tRNA synthetase and some endoplasmic reticulum antigens retained approximately their normal distribution in the cell. Double fluorochrome staining showed no morphological association of methionyl-tRNA synthetase with the microtubule, actin, or cytokeratin fiber systems of PtK2 cells. These observations demonstrate that detergent-insoluble cellular components, sometimes referred to as "cytoskeletal" preparations, contain significant amounts of nonfilamentous material including ribosomes, and membrane residue. Caution is required in speculating about intermolecular associations in such a complex cell fraction.

scholarly journals Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis

2021 ◽  
pp. 2101554
Author(s):  
Alice Hadchouel ◽  
David Drummond ◽  
Clément Pontoizeau ◽  
Laura Aoust ◽  
Maria-Margarita Hurtado Nedelec ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Alveolar Proteinosis ◽  
Growth Failure ◽  
Reactive Oxygen ◽  
Lung Lavage ◽  
Trna Synthetase ◽  
Growth Delay ◽  
Oxygen Species ◽  
Methionine Supplementation ◽  
Alveolar Proteinosis

IntroductionPulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase (MARS1) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease.MethodsFour patients received methionine supplementation and were followed for respiratory, hepatic, growth, and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species (ROS) production by patient monocytes before and after methionine supplementation was also studied.ResultsMethionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material, and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or non-invasive ventilation could be weaned off within 60 days. Liver dysfunction, inflammation, and growth delay also improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes.ConclusionMethionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the MARS1 gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.

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