Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2
Open accessAbstract
Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. However, signaling pathways acting downstream of MEF2 are largely unknown. Here, we performed a microarray analysis using Mef2c -null mouse embryos and identified a novel MEF2-regulated gene encoding a muscle-specific protein kinase, Srpk3, belonging to the serine arginine protein kinase (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins. The Srpk3 gene is specifically expressed in the heart and skeletal muscle from embryogenesis to adulthood and is controlled by a muscle-specific enhancer directly regulated by MEF2. Srpk3 -null mice display a new entity of type 2 fiber-specific myopathy with a marked increase in centrally placed nuclei; while transgenic mice overexpressing Srpk3 in skeletal muscle show severe myofiber degeneration and early lethality. We conclude that normal muscle growth and homeostasis require MEF2-dependent signaling by Srpk3.
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Top enriched pathways for hypertrophic cardiomyopathy pointed to candidate cardiomyocyte-specific therapeutic targets including ADCY5 and druggable targets including SRPK3.
“Top enriched pathways for hypertrophic cardiomyopathy pointed to candidate cardiomyocyte-specific therapeutic targets including ADCY5, disruption of which is associated with longevity and protection against cardiomyopathy in mouse models40, as well as druggable targets41 including SRPK3, a downstream effector of MEF242 which is known to play a critical role in myocardial cell hypertrophy43.”
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Molecular Recognition by LARGE Is Essential for Expression of Functional Dystroglycan
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Transfer learning enables predictions in network biology
Theodoris, C. V., Xiao, L., Chopra, A., Chaffin, M. D., Al Sayed, Z. R., Hill, M. C., Mantineo, H., Brydon, E. M., Zeng, Z., Liu, X. S., et al. (2023) · Nature · doi:10.1038/s41586-023-06139-9 · Cited by 1,193 · see citing works
- Authors
- Nakagawa, O., Arnold, M., Nakagawa, M., Hamada, H., Shelton, J. M., Kusano, H., Harris, T. M., Childs, G., Campbell, K. P., Richardson, J. A., Nishino, I., & Olson, E. N.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Iowa (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-09-01
- Volume
- 19
- Issue
- 17
- Pages
- 2066-2077
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1199576
- OpenAlex
- W2152010440
- Cited by
- 125
- References
- 1
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 18 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 5
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Welch Foundation
- Muscular Dystrophy Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL083488)
- National Institute of General Medical Sciences (T-32-GM08014, T32GM008014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- centronuclear myopathy, MEF2, serine-arginine protein kinase, muscle-specific enhancer, myofiber degeneration, skeletal muscle development, transgenic overexpression
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, DNA, DNA-Binding Proteins, Enhancer Elements, Genetic, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Transcription Factors, Transcription, Genetic, Signal Transduction, Gene Expression Regulation, Enzymologic, Protein Serine-Threonine Kinases, Myogenic Regulatory Factors, Mice, Knockout, Muscle, Skeletal, Gene Expression Regulation, Developmental, Gene Expression Profiling, Myopathies, Structural, Congenital, Mice, MEF2 Transcription Factors
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