PXD024631

PXD024631 is an original dataset announced via ProteomeXchange.

Title	STARS overexpression in the mdx mouse tibialis anterior muscle increases maximal isometric force production and regulates members of the keratin, NRF2 and OXPHOS pathways
Description	Duchenne muscular dystrophy (DMD) is characterized by impaired cytoskeleton organization, cytosolic calcium handling oxidative stress and mitochondrial dysfunction. This results in progressive and fatal muscle damage, wasting and weakness. The Striated Muscle activator of Rho signalling (STARS) is an actin binding protein that activates the myocardin-related transcription factor-A (MRTFA)/serum response factor (SRF) transcriptional pathway; a pathway that regulates cytoskeletal structure, muscle function, growth and repair. Here we investigated the regulation of several members of the STARS signalling pathway in muscle from patients with DMD and the dystrophin-deficient mdx and dko (utrophin‐ and dystrophin‐null) mice. A reduction in protein levels of STARS, SRF and RHOA, and an increase in MRTFA were observed in quadriceps muscle of patients with DMD. STARS, SRF and MRTFA mRNA levels were also decreased in DMD muscle, while Stars mRNA levels were decreased in mdx tibialis anterior (TA) muscle and Srf and Mrtfa mRNAs were decreased in dko TA muscle. Overexpressing the human STARS (hSTARS) protein in mdx TA muscle increased maximal isometric specific force by 13%. This was not associated with changes in muscle mass, fibre cross-sectional area (CSA), fibre type, centralized nuclei or collagen deposition. Proteomics screening identified 31 upregulated and 22 downregulated proteins or individual peptides that were significantly regulated by hSTARS overexpression. Pathway enrichment analysis indicated that hSTARS overexpression regulated the keratin, NRF2 and oxidative phosphorylation (OXPHOS) pathways. These pathways are impaired in dystrophic muscle and regulate cytoskeleton organization, oxidative stress and mitochondrial energy production; processes that are vital for muscle function. We conclude that increasing the STARS protein in dystrophic muscle improves muscle force production, potentially via its regulation of multiple pathways that positively influence cytoskeletal structure, oxidative stress and energy production.
HostingRepository	PRIDE
AnnounceDate	2021-08-12
AnnouncementXML	Submission_2021-08-12_04:44:57.747.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-10 02:20:51	ID requested
⏵ 1	2021-08-12 04:44:58	announced

Sadler KJ, Gatta PAD, Naim T, Wallace MA, Lee A, Zaw T, Lindsay A, Chung RS, Bello L, Pegoraro E, Lamon S, Lynch GS, Russell AP, Striated muscle activator of Rho signalling (STARS) overexpression in the mdx mouse enhances muscle functional capacity and regulates the actin cytoskeleton and oxidative phosphorylation pathways. Exp Physiol, 106(7):1597-1611(2021) [pubmed]

submitter keyword: skeletal muscle, muscular dystrophy, mdx mouse, adeno-associated virus, STARS, keratin, NRF2, OXPHOS

Albert Lee
contact affiliation	Centre for MND Research, Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, 2109 Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024631
     1. Label: PRIDE project
     2. Name: STARS overexpression in the mdx mouse tibialis anterior muscle increases maximal isometric force production and regulates members of the keratin, NRF2 and OXPHOS pathways