PXD037630 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A non-canonical function of tyrosyl-tRNA synthetase in actin bundling |
Description | Aminoacyl-tRNA synthetases are the largest protein family implicated in Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy that is currently incurable. These essential enzymes catalyze the attachment of amino acids to their cognate tRNAs, thereby enabling the protein biosynthesis in every cell. Surprisingly, loss of aminoacylation is not a prerequisite for CMT to occur, suggesting a disease mechanism associated with a gain of neurotoxic function. Via an unbiased genetic modifier screen in a Drosophila model of tyrosyl-tRNA synthetase (YARS) -induced CMT, we established a link between the tRNA-ligase and regulators of actin cytoskeleton. By investigating the interactome of YARS in cellulo we found this synthetase to be enriched in protein complexes containing actin and actin-modifying proteins. Follow up in vitro and in vivo studies demonstrated that YARS itself has not only actin binding- but also actin-bundling properties independent of its aminoacylation function. These non-canonical activities are evolutionary conserved and contribute to the organization of actin cytoskeleton in Drosophila neurons and in patient-derived cells. An enzymatically active YARSCMT mutant caused stronger actin bundling in vitro, disorganization of actin bundle-rich stress fibers in patient-derived cells and impaired multiple actin-based steps of the synaptic vesicle cycle in fly neurons. Genetic modulation of the F-actin organization state restored synaptic vesicle mobility and rescued hallmark electrophysiological and morphological features in the neurons of fruit flies expressing different YARSCMT mutations. Thus, we uncover a role of tyrosyl-tRNA synthetase in actin organization that is implicated in the CMT neuropathy. |
HostingRepository | PRIDE |
AnnounceDate | 2023-01-09 |
AnnouncementXML | Submission_2023-01-09_06:41:29.006.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | SeyyyedmohsenHosseinibarkooie |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-10-20 13:45:36 | ID requested | |
⏵ 1 | 2023-01-09 06:41:29 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: YARS,HEK293t cells |
Contact List
AlbenaJordanova |
contact affiliation | VIB-UAntwerp Center for Molecular Neurology, University of Antwerp, Antwerpen, Belgium Department of Medical Chemistry and Biochemistry, Medical University-Sofia, Sofia, Bulgaria |
contact email | Albena.Jordanova@uantwerpen.vib.be |
lab head | |
SeyyyedmohsenHosseinibarkooie |
contact affiliation | University of Virginia |
contact email | sh4hj@virginia.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037630
- Label: PRIDE project
- Name: A non-canonical function of tyrosyl-tRNA synthetase in actin bundling