PXD043917

PXD043917 is an original dataset announced via ProteomeXchange.

Title	Neddylation is a global orchestrator of the molecular network driving Schwann cell myelination
Description	Axonal myelination is essential for neuronal function and health. In peripheral nerves, deficient myelination is responsible for the morbidity of various forms of inherited or acquired neuropathies, including Charcot-Marie-Tooth disease and diabetic neuropathy. Decades of research have uncovered a complex transcriptional and post-transcriptional program that co-ordinates the formation and maintenance of the myelin sheath. In contrast, much less is known about the functional role of post-translational modification (PTM) of proteins in this remarkable biogenic process. Neddylation, a PTM that involves the conjugation of the ubiquitin-like protein Nedd8 to protein targets, has recently emerged as a central and versatile regulator of many cellular processes, including gene transcription, metabolism, and cellular differentiation. In this study, we show that genetic and pharmacological inhibition of neddylation in vivo in developing Schwann cells lead to striking nerve defects that exhibit the classical hallmarks of a severe neuropathy, including gait abnormalities, muscle weakness, and hindlimb clasping, ultimately leading to early death. The mutant mice lack peripheral myelin and develop secondary axonal loss, and we demonstrate, at the mechanistic level, that neddylation regulates multiple critical myelination-related pathways. Together, our findings identify neddylation as a central regulatory hub of control of peripheral myelination and delineate the potential pathogenetic mechanisms in inherited human PNS disorders, characterized by mutations in genes related to the neddylation pathway.
HostingRepository	PRIDE
AnnounceDate	2024-06-16
AnnouncementXML	Submission_2024-06-16_01:57:50.488.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043917
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	neddylated lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-19 07:39:36	ID requested
⏵ 1	2024-06-16 01:57:51	announced

10.1126/sciadv.adm7600;

10.6019/PXD043917;

Ayuso-Garc, í, a P, S, á, nchez-Rueda A, Velasco-Avil, é, s S, Tamayo-Caro M, Ferrer-Pin, ó, s A, Huarte-Sebastian C, Alvarez V, Riobello C, Jim, é, nez-Vega S, Buendia I, Ca, ñ, as-Martin J, Fern, á, ndez-Susavila H, Aparicio-Rey A, Esquinas-Rom, á, n EM, Ponte CR, Guhl R, Laville N, P, é, rez-Andr, é, s E, Lav, í, n JL, Gonz, á, lez-Lopez M, C, á, mara NM, Aransay AM, Lozano JJ, Sutherland JD, Barrio R, Martinez-Chantar ML, Azkargorta M, Elortza F, Soriano-Navarro M, Matute C, S, á, nchez-G, ó, mez MV, Bay, ó, n-Cordero L, P, é, rez-Samart, í, n A, Bravo SB, Kurz T, Lama-D, í, az T, Blanco MG, Haddad S, Record CJ, van Hasselt PM, Reilly MM, Varela-Rey M, Woodhoo A, Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination. Sci Adv, 10(15):eadm7600(2024) [pubmed]

submitter keyword: PTMs,Neddylation, ubiquitin-like, Schwann cells, label free

Felix Elortza
contact affiliation	Proteomics Service CIC bioGUNE Bizkaia Tech. Park. Build. 800 Derio 48160 Spain
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD043917

PRIDE project URI

• PRIDE
  1. PXD043917
     1. Label: PRIDE project
     2. Name: Neddylation is a global orchestrator of the molecular network driving Schwann cell myelination