PXD022414
PXD022414 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Cardiomyocyte Contractile Impairment in Heart Failure Results from Reduced BAG3-mediated Sarcomeric Protein Turnover |
| Description | The association between reduced myofilament force-generating capacity (Fmax) and heart failure (HF) is clear, however the underlying molecular mechanisms are poorly understood. Here, we show impaired Fmax arises from reduced BAG3-mediated sarcomere turnover. Myofilament BAG3 expression decreases in human HF and positively correlates with Fmax. We confirmed this relationship using BAG3+/- mice, which had reduced Fmax and increased myofilament ubiquitination, suggesting impaired protein turnover. We show cardiac BAG3 operates via chaperone-assisted selective autophagy (CASA), conserved from skeletal muscle, and confirm sarcomeric CASA complex localization is BAG3/proteotoxic stress-dependent. Using mass spectrometry, we characterize the myofilament CASA interactome in the human heart and identify eight clients of BAG3-mediated protein turnover. To determine if increasing BAG3 expression in HF can restore sarcomere proteostasis/Fmax, HF mice were treated with AAV9-BAG3. Gene therapy fully rescued Fmax and CASA protein turnover after four weeks. Our findings identify BAG3-mediated sarcomere turnover is fundamental for myofilament functional maintenance. |
| HostingRepository | MassIVE |
| AnnounceDate | 2021-03-16 |
| AnnouncementXML | Submission_2021-03-16_10:57:57.688.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Thomas Martin |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | GG; Phospho |
| Instrument | LTQ XL |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2020-11-06 14:11:57 | ID requested | |
| ⏵ 1 | 2021-03-16 10:57:58 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Heart failure, sarcomere, ubiquitination, protein turnover |
Contact List
| Jonathan Kirk | |
|---|---|
| contact affiliation | Loyola University Chicago |
| contact email | jkirk2@luc.edu |
| lab head | |
| Thomas Martin | |
| contact affiliation | Loyola University Chicago |
| contact email | tmartin7@luc.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/MSV000086422/ |
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