PXD008145

PXD008145 is an original dataset announced via ProteomeXchange.

Title	Skeletal muscle-specific methyltransferase METTL21C trimethylates p97 and regulates autophagy-associated protein breakdown
Description	Protein aggregates and cytoplasmic vacuolization are major hallmarks of multisystem proteinopathies (MSP) that lead to muscle weakness. Here, we identify METTL21C as a novel skeletal muscle-specific lysine methyltransferase. Insertion of a -galactosidase cassette into the Mettl21c mouse locus revealed METTL21C is specifically expressed in MYH7 positive skeletal muscle fibers. Ablation of the Mettl21c gene reduced endurance capacity and led to accumulation of cellular residuals due to incomplete autophagy in the skeletal muscle of Mettl21c-/- mutants during aging. Moreover, denervation-induced muscle atrophy highlighted further impairments of autophagy-related proteins, including LC3, p62, and cathepsins in Mettl21c-/- muscles. In addition, we demonstrate METTL21C interacts with the ATPase p97 (VCP), which is mutated in various human MSP conditions. We also reveal METTL21C trimethylates p97 on Lys315 residue, and found loss of this modification reduced p97 hexamer formation and ATPase activity in vivo. We conclude the methyltransferase METTL21C is an important modulator of protein degradation in skeletal muscle under both normal and enhanced protein breakdown conditions due to its ability to trimethylate and regulate p97.
HostingRepository	PRIDE
AnnounceDate	2018-05-04
AnnouncementXML	Submission_2018-05-04_04:47:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janica Wiederstein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; dimethylated L-arginine; N6: N6; N6: N6-dimethyl-L-lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-06 23:42:19	ID requested
1	2018-05-04 02:09:14	announced
⏵ 2	2018-05-04 04:47:04	announced	Updated publication reference for PubMed record(s): 29719249.

Wiederstein JL, Nolte H, G, ü, nther S, Piller T, Baraldo M, Kostin S, Bloch W, Schindler N, Sandri M, Blaauw B, Braun T, H, ö, lper S, Kr, ü, ger M, Skeletal Muscle-Specific Methyltransferase METTL21C Trimethylates p97 and Regulates Autophagy-Associated Protein Breakdown. Cell Rep, 23(5):1342-1356(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Methylation, proteomics, proteostasis

Marcus Krüger
contact affiliation	CECAD/Institute for Genetics, University of Cologne, Cologne, Germany
contact email	marcus.krueger@uni-koeln.de
lab head
Janica Wiederstein
contact affiliation	Institute for Genetics/CECAD (AG Krüger)
contact email	jwieders@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008145
     1. Label: PRIDE project
     2. Name: Skeletal muscle-specific methyltransferase METTL21C trimethylates p97 and regulates autophagy-associated protein breakdown