PXD022997

PXD022997 is an original dataset announced via ProteomeXchange.

Title	Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation
Description	The fast skeletal muscle protein α-actinin-3 is absent in 1.5 billion people worldwide due to homozygosity for a nonsense polymorphism in the ACTN3 gene (R577X). The prevalence of the 577X allele increased as modern humans moved to colder climates, suggesting a link between α-actinin-3 deficiency and improved cold tolerance. Here, we show that humans lacking α-actinin-3 (XX) are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis. Muscles of XX individuals displayed a shift towards more slow-twitch isoforms of myosin heavy chain (MyHC) and sarcoplasmic reticulum (SR) proteins, accompanied by altered neuronal muscle activation resulting in increased tone rather than overt shivering. Experiments on Actn3 knockout mice showed no alterations in brown adipose tissue (BAT) properties that could explain the improved cold tolerance in XX individuals. Thus, this study provides a clear mechanism for the positive selection of the ACTN3 X-allele in cold climates and supports a key thermogenic role of skeletal muscle during cold exposure in humans.
HostingRepository	PRIDE
AnnounceDate	2021-03-17
AnnouncementXML	Submission_2021-03-16_23:21:26.744.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JIMMY RODRIGUEZ
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-08 07:29:13	ID requested
1	2021-03-16 03:42:06	announced
⏵ 2	2021-03-16 23:21:27	announced	2021-03-17: Updated project metadata.

10.1016/J.AJHG.2021.01.013;

Wyckelsma VL, Venckunas T, Houweling PJ, Schlittler M, Lauschke VM, Tiong CF, Wood HD, Ivarsson N, Paulauskas H, Eimantas N, Andersson DC, North KN, Brazaitis M, Westerblad H, -actinin-3 during human evolution provides superior cold resilience and muscle heat generation. Am J Hum Genet, 108(3):446-457(2021) [pubmed]

submitter keyword: α-actinin, evolution, muscle

Hakan Westerblad
contact affiliation	Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
contact email	hakan.westerblad@ki.se
lab head
JIMMY RODRIGUEZ
contact affiliation	Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	esneider007@gmail.com
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/2021/03/PXD022997

PRIDE project URI

• PRIDE
  1. PXD022997
     1. Label: PRIDE project
     2. Name: Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation