File Download

There are no files associated with this item.

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
Related Researcher

명경재

Myung, Kyungjae
Center for Genomic Integrity
Read More

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons

Author(s)
Antonellis, AnthonyLee-Lin, Shih-QueenWasterlain, AmyLeo, PaulQuezado, MarthaGoldfarb, Lev G.Myung, KyungjaeBurgess, ShawnFischbeck, Kenneth H.Green, Eric D.
Issued Date
2006-10
DOI
10.1523/JNEUROSCI.1671-06.2006
URI
https://scholarworks.unist.ac.kr/handle/201301/31068
Fulltext
https://www.jneurosci.org/content/26/41/10397
Citation
JOURNAL OF NEUROSCIENCE, v.26, no.41, pp.10397 - 10406
Abstract
Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more severe in the upper extremities. We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is a member of the family of aminoacyl-tRNA synthetases responsible for charging tRNA with cognate amino acids; GARS ligates glycine to tRNAGly. Here, we present functional analyses of disease-associated GARS mutations and show that there are not any significant mutation-associated changes in GARS expression levels; that the majority of identified GARS mutations modeled in yeast severely impair viability; and that, in most cases, mutant GARS protein mislocalizes in neuronal cells. Indeed, four of the five mutations studied show loss-of-function features in at least one assay, suggesting that tRNA-charging deficits play a role in disease pathogenesis. Finally, we detected endogenous GARS-associated granules in the neurite projections of cultured neurons and in the peripheral nerve axons of normal human tissue. These data are particularly important in light of the recent identification of CMT-associated mutations in another tRNA synthetase gene [YARS(tyrosyl-tRNA synthetase gene)]. Together, these findings suggest that tRNA-charging enzymes play a key role in maintaining peripheral axons.
Publisher
SOC NEUROSCIENCE
ISSN
0270-6474
Keyword (Author)
Charcot-Marie-Tooth diseasespinal muscular atrophyperipheral neuropathyaxonopathytRNA synthetaseaxonal translation
Keyword
MARIE-TOOTH-DISEASESPINAL MUSCULAR-ATROPHYSACCHAROMYCES-CEREVISIAEPARKIN SUBSTRATECHROMOSOME 7PMOTORPROTEINNEUROPATHYNEURONCOMPLEX

qrcode

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.