PXD038754

PXD038754 is an original dataset announced via ProteomeXchange.

Title	Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules
Description	Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2 neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology is inexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that upon environmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where they aberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated from the cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding to G3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting this aberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stress-dependent molecular link across diverse CMT2 mutants and provide a conceptual framework for understanding genetic heterogeneity in light of environmental stress.
HostingRepository	iProX
AnnounceDate	2022-12-13
AnnouncementXML	Submission_2023-02-08_22:34:59.747.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qinqin Cui
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-12 19:05:32	ID requested
1	2023-02-05 19:18:27	announced
⏵ 2	2023-02-08 22:35:01	announced	2023-02-09: Update publication information.

Cui Q, Bi H, Lv Z, Wu Q, Hua J, Gu B, Huo C, Tang M, Chen Y, Chen C, Chen S, Zhang X, Wu Z, Lao Z, Sheng N, Shen C, Zhang Y, Wu ZY, Jin Z, Yang P, Liu H, Li J, Bai G, Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules. Cell, 186(4):803-820.e25(2023) [pubmed]

submitter keyword: Charcot-Marie-Tooth neuropathies, stress granule, motor neuron, genetic heterogeneity

Ge Bai
contact affiliation	Zhejiang University
contact email	gebai@zju.edu.cn
lab head
Qinqin Cui
contact affiliation	Zhejiang University
contact email	cuiqin0704@163.com
dataset submitter

iProX dataset URI