The Role of Integrin β1D Mislocalization in the Pathophysiology of Calpain 3-Related Limb-Girdle Muscular Dystrophy
Valls-Mateu, Aida (Instituto de Salud Carlos III)
Ruiz-Roldán, C. (Instituto de Investigación Biogipuzkoa)
Immanuel, J. (Instituto de Salud Carlos III)
Alonso-Martín, S. (Instituto de Investigación Biogipuzkoa)
Gallardo, Eduard (Institut de Recerca Sant Pau)
Fernandez-Torron, Roberto (Hospital de Donostia (Sant Sebastià, País Basc))
Bonilla, M. (Organización Sanitaria Integrada Donostialdea)
Lersundi, A. (Universidad del País Vasco)
Hernández-Laín, A. (Universidad Complutense de Madrid)
Domínguez-González, Cristina (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Vílchez, J.J. (Hospital Universitari i Politècnic La Fe (València))
Iruzubieta, P. (McGill University)
López de Munain, A. (University of Deusto)
Sáenz, A. (Instituto de Salud Carlos III)
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	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 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.
Grants:	Instituto de Salud Carlos III PI21/00047
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	LGMDR1 ; Calpain 3 ; Costamere ; Integrin β1 ; Limb-girdle muscular dystrophy
Published in:	Cells, Vol. 14 Núm. 6 (march 2025) , p. 446, ISSN 2073-4409

DOI: 10.3390/cells14060446
PMID: 40136695

35 p, 30.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles