The Role of Integrin ß1D 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 CAPN3 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 obse...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2025 |
| Country: | España |
| Institution: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repository: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p19530 |
| Online Access: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19530 |
| Access Level: | Open access |
| Keyword: | limb-girdle muscular dystrophy LGMDR1 calpain 3 integrin beta 1 costamere |
| Summary: | Limb-girdle muscular dystrophy R1 (LGMDR1) is characterized by progressive proximal muscle weakness due to mutations in the CAPN3 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 beta 1D isoform (ITG beta 1D) 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. |
|---|