PXD039284-1
PXD039284 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Cardiomyocyte external mechanical unloading activates modifications of alpha-actinin differently from sarcomere-originated unloading |
| Description | Loss of myocardial mass in a neonatal rat cardiomyocyte culture is studied to determine whether there is a distinguishable cellular response based on the origin of mechano-signals. The approach herein compares the sarcomeric assembly and disassembly processes in heart cells by imposing mechano-signals at the interface with the extracellular matrix (extrinsic) and at the level of the myofilaments (intrinsic). Experiments compared the effects of imposed internal (inside/out) and external (outside/in) loading and unloading on modifications in neonatal rat cardiomyocytes. Unloading of the cellular substrate by myosin inhibition (1?M mavacamten), or cessation of cyclic strain (1 Hz, 10% strain) after preconditioning, led to significant disassembly of sarcomeric ?-actinin by 6 hrs. In myosin inhibition, this was accompanied by redistribution of intracellular poly-ubiquitin K48 to the cellular periphery relative to the poly-ubiquitin K48 reservoir at the I-band. Moreover, loading and unloading of the cellular substrate led to a three-fold increase in post translational modifications (PTMs) when compared to the myosin-specific activation or inhibition. Specifically, phosphorylation increased with loading while ubiquitination increased with unloading, which may involve ERK1/2 and FAK activation. The identified PTMs, including ubiquitination, acetylation, and phosphorylation, are proposed to modify internal domains in ?-actinin to increase its propensity to bind F-actin. These results demonstrate a link between mechanical feedback and sarcomere protein homeostasis via PTMs of ?-actinin that exemplify how cardiomyocytes exhibit differential responses to the origin of force. The implications of sarcomere regulation governed by PTMs of ?-actinin are discussed with respect to cardiac atrophy and heart failure. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-07-20 |
| AnnouncementXML | Submission_2023-07-20_09:54:03.013.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Chad M. Warren |
| SpeciesList | scientific name: Rattus norvegicus; common name: Norway rat; NCBI TaxID: 10116; |
| ModificationList | Phospho; Acetyl; GG |
| Instrument | timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-01-05 06:39:25 | ID requested | |
| ⏵ 1 | 2023-07-20 09:54:03 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: HCM, DCM, HFpEF, HFrEF, omecamtiv mecarbil, Flexcell |
Contact List
| Brenda Russell | |
|---|---|
| contact affiliation | University of Illinois at Chicago |
| contact email | russell@uic.edu |
| lab head | |
| Chad M. Warren | |
| contact affiliation | University of Illinois-Chicago |
| contact email | cmwarren@uic.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/MSV000091010/ |
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