ArticleMolecular biology of the cell2009
The rho-guanine nucleotide exchange factor domain of obscurin activates rhoA signaling in skeletal muscle.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- Obscurin a localizes near the cell membrane to modulate stress fiber dynamics and cell migration.The Journal of biological chemistry · 2026Article
- The varied functions of the giant muscle scaffold protein obscurin.Frontiers in cell and developmental biology · 2025Review
- The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers.Biological research · 2024Article
- Identification of Giant Isoforms of Obscurin in Rat Striated Muscles Using Polyclonal Antibodies.Bulletin of experimental biology and medicine · 2024Article
- Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.JCI insight · 2024Article
- A Perspective on Developing Modeling and Image Analysis Tools to Investigate Mechanosensing Proteins.Integrative and comparative biology · 2023Article
- Multi-omics analysis of sarcospan overexpression in mdx skeletal muscle reveals compensatory remodeling of cytoskeleton-matrix interactions that promote mechanotransduction pathways.Skeletal muscle · 2023Article
- Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Giant obscurin regulates migration and metastasis via RhoA-dependent cytoskeletal remodeling in pancreatic cancer.Cancer letters · 2022Article
- Review
- Obscurin: A multitasking giant in the fight against cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- The pathophysiological nature of sarcomeres in trigger points in patients with myofascial pain syndrome: A preliminary study.European journal of pain (London, England) · 2020Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.Scientific reports · 2020Article
- The M-band: The underestimated part of the sarcomere.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Proteomic Analysis of Myocardia Containing the Obscurin R4344Q Mutation Linked to Hypertrophic Cardiomyopathy.Frontiers in physiology · 2020Article
- Article
- Unraveling obscurins in heart disease.Pflugers Archiv : European journal of physiology · 2019Review
- Thick Filament Protein Network, Functions, and Disease Association.Comprehensive Physiology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Obscurin is a large ( approximately 800-kDa), modular protein of striated muscle that concentrates around the M-bands and Z-disks of each sarcomere, where it is well positioned to sense contractile activity. Obscurin contains several signaling domains, including a rho-guanine nucleotide exchange factor (rhoGEF) domain and tandem pleckstrin homology domain, consistent with a role in rho signaling in muscle. We investigated the ability of obscurin's rhoGEF domain to interact with and activate small GTPases. Using a combination of in vitro and in vivo approaches, we found that the rhoGEF domain of obscurin binds selectively to rhoA, and that rhoA colocalizes with obscurin at the M-band in skeletal muscle. Other small GTPases, including rac1 and cdc42, neither associate with the rhoGEF domain of obscurin nor concentrate at the level of the M-bands. Furthermore, overexpression of the rhoGEF domain of obscurin in adult skeletal muscle selectively increases rhoA expression and activity in this tissue. Overexpression of obscurin's rhoGEF domain and its effects on rhoA alter the expression of rho kinase and citron kinase, both of which can be activated by rhoA in other tissues. Injuries to rodent hindlimb muscles caused by large-strain lengthening contractions increases rhoA activity and displaces it from the M-bands to Z-disks, similar to the effects of overexpression of obscurin's rhoGEF domain. Our results suggest that obscurin's rhoGEF domain signals at least in part by inducing rhoA expression and activation, and altering the expression of downstream kinases in vitro and in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.