mTORC1 and nuclear ERK spatially control translation in cardiomyocytes through 4EBP1 phosphorylation
was necessary and sufficient to relocalize translation initiation sites closer to the nuclei. ERK activation drove redistribution of ribosomes and nascent translation toward the center of the cardiomyocyte without altering global mRNA distribution, leading to spatially enriched deposition of new sarcomeric protein in the cardiomyocyte interior. Together, these findings demonstrate that global protein synthesis can be spatially regulated by the activation of different kinases in distinct subcellular compartments and identify a mechanism that drives concentric hypertrophy.
Authors
- Benjamin L. Prosser (ORCID: https://orcid.org/0000-0003-3696-9131)
- Daniel P. Kelly (ORCID: https://orcid.org/0000-0002-3811-9491)
- Elizabeth Pruzinsky (ORCID: https://orcid.org/0000-0001-9330-5329)
- Izhak Kehat (ORCID: https://orcid.org/0000-0002-4388-1579)
- Jonathan J. Edwards (ORCID: https://orcid.org/0000-0002-8153-7066)
- Keita Uchida (ORCID: https://orcid.org/0000-0001-8458-9796)
- Emily A. Scarborough (ORCID: https://orcid.org/0000-0001-5774-9731)
- Hali Hartman
Institutions
- Children's Hospital of Philadelphia (US)
- Rappaport Family Institute for Research in the Medical Sciences (IL)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Signaling
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1126/scisignal.adu5769
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- American Heart Association
- United States - Israel Binational Science Foundation
- Children's Hospital of Philadelphia
- Fondation Leducq
- National Institutes of Health