The Role of Integrin β1D Mislocalization in the Pathophysiology of Calpain 3-Related Limb–Girdle Muscular Dystrophy
Limb-girdle muscular dystrophy R1 (LGMDR1) is characterized by progressive proximal muscle weakness due to mutations in the <i>CAPN3</i> gene. Little is known about CAPN3's function in muscle, but its loss results in aberrant sarcomere formation. Human muscle structure was analyzed in this study, with observations including integrin β1D isoform (ITGβ1D) mislocalization, a lack of Talin-1 (TLN1) in the sarcolemma and the irregular expression of focal adhesion kinase (FAK) in LGMDR1 muscles, suggesting a lack of integrin activation with an altered sarcolemma, extracellular matrix (ECM) assembly and signaling pathway deregulation, which may cause frailty in LGMDR1 muscle fibers. Additionally, altered nuclear morphology, centrosome distribution and microtubule organization have been found in muscle cells derived from LGMDR1 patients.
Authors
- Jenita Immanuel (ORCID: https://orcid.org/0000-0002-7236-1855)
- Andrea Valls (ORCID: https://orcid.org/0000-0002-9211-4034)
- Amets Sáenz (ORCID: https://orcid.org/0000-0002-0704-1150)
- Pablo Iruzubieta (ORCID: https://orcid.org/0000-0003-0331-6222)
- Cristina Domínguez‐González (ORCID: https://orcid.org/0000-0001-5151-988X)
- Sonia Alonso‐Martín (ORCID: https://orcid.org/0000-0002-3254-0365)
- Eduard Gallardo (ORCID: https://orcid.org/0000-0002-3942-3436)
- Juan J. Vílchez (ORCID: https://orcid.org/0000-0002-0532-2872)
- Roberto Fernández‐Torrón (ORCID: https://orcid.org/0000-0002-2202-8165)
- Aurelio Hernández‐Laín (ORCID: https://orcid.org/0000-0003-1642-4505)
- Ana Lersundi (ORCID: https://orcid.org/0000-0002-6207-1926)
- Cristina Ruiz‐Roldán
- Mario Bonilla (ORCID: https://orcid.org/0000-0001-6205-466X)
- Adolfo López de Munain
Institutions
- Universidad Complutense de Madrid (ES)
- Montreal Neurological Institute and Hospital (CA)
- Universidad de Deusto (ES)
- University of the Basque Country (ES)
- Instituto de Salud Carlos III (ES)
- Hospital de Sant Pau (ES)
- Hospital Universitari i Politècnic La Fe (ES)
- Research Institute Hospital 12 de Octubre (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Biogipuzkoa Health Research Institute (ES)
- Hospital Universitario 12 De Octubre (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Policlínica Gipuzkoa (ES)
- Osakidetza (ES)
- Instituto de Investigación Sanitaria La Fe (ES)
- Institut de Recerca Sant Pau (ES)
- McGill University (CA)
Publication Details
- Journal
- Cells
- Published
- 2025-03-17
- DOI
- https://doi.org/10.3390/cells14060446
- Citations
- 3
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Association Française contre les Myopathies
- Instituto de Salud Carlos III