PXD012405

PXD012405 is an original dataset announced via ProteomeXchange.

Title	Environmental Arginine Controls Multinuclear Giant Cell Metabolism and Formation
Description	Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. Formation of MGCs is energy intensive to enforce membrane fusion and cytoplasmic expansion. Here we used receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation. We found amino acid (AA) scarcity controls MGC formation and reveal specific requirements for extracellular arginine in RANKL cellular programming. Indeed, systemic arginine restriction improved outcome in multiple murine arthritis models, by inducing preosteoclast metabolic quiescence, associated with a dysregulated tricarboxylic acid (TCA) cycle, and diverted metabolic fluxes from central metabolic pathways independent of mTORC1 activity or global transcriptional and translational inhibition. A conserved metabolic mechanism occurred in IL-4 induced MGCs. Strikingly, we demonstrate that restriction of multiple AAs triggered metabolic adaptation and blocked MGC formation and each was rescued by their downstream metabolites. These data establish how environmental nutrients control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodeling.
HostingRepository	PRIDE
AnnounceDate	2019-12-18
AnnouncementXML	Submission_2020-01-29_06:29:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-17 02:28:24	ID requested
1	2019-12-17 07:20:20	announced
2	2019-12-18 07:08:19	announced	2019-12-18: Updated project metadata.
⏵ 3	2020-01-29 06:29:58	announced	2019-12-18: Updated project metadata. 2020-01-29: Updated publication reference for PubMed record(s): 31969567.

Brunner JS, Vulliard L, Hofmann M, Kieler M, Lercher A, Vogel A, Russier M, Br, ü, ggenthies JB, Kerndl M, Saferding V, Niederreiter B, Junza A, Frauenstein A, Scholtysek C, Mikami Y, Klavins K, Kr, ö, nke G, Bergthaler A, O'Shea JJ, Weichhart T, Meissner F, Smolen JS, Cheng P, Yanes O, Menche J, Murray PJ, Sharif O, Bl, ü, ml S, Schabbauer G, Environmental arginine controls multinuclear giant cell metabolism and formation. Nat Commun, 11(1):431(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Arginine, Preosteoclasts, RANKL, LC-MS

Gernot Schabbauer
contact affiliation	Institute for Vascular Biology, Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria
contact email	gernot.schabbauer@meduniwien.ac.at
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2019/12/PXD012405

PRIDE project URI

• PRIDE
  1. PXD012405
     1. Label: PRIDE project
     2. Name: Environmental Arginine Controls Multinuclear Giant Cell Metabolism and Formation