The Role of Integrin ß1D Mislocalization in the Pathophysiology of Calpain 3-Related Limb-Girdle Muscular Dystrophy
Por:
Valls, A, Ruiz-Roldán, C, Immanuel, J, Alonso-Martín, S, Gallardo, E, Fernández-Torrón, R, Bonilla, M, Lersundi, A, Hernández-Laín, A, Domínguez-González, C, Vílchez, JJ, Iruzubieta, P, de Munain, AL, Sáenz, A
Publicada:
17 mar 2025
Resumen:
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.
Filiaciones:
Valls, A:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Ruiz-Roldán, C:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Immanuel, J:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Alonso-Martín, S:
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Biogipuzkoa Hlth Res Inst, Stem Cells & Aging Grp, Bioengn Area, San Sebastian 20014, Spain
Gallardo, E:
Hosp Santa Creu i St Pau, Dept Genet, Barcelona, Spain
Inst Recerca St Pau IR StPau, Barcelona 08041, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Carlos Hlth Inst 3, Spanish Minist Sci & Innovat, Madrid 28029, Spain
Fernández-Torrón, R:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Univ Donostia, Osakidetza, Dept Neurol, E-20014 San Sebastian, Guipuzcoa, Spain
Bonilla, M:
Biogipuzkoa Hlth Res Inst, Stem Cells & Aging Grp, Bioengn Area, San Sebastian 20014, Spain
Osakidetza, Donostialdea Integrated Hlth Org, Dept Traumatol, San Sebastian, Spain
Lersundi, A:
Osakidetza, Donostialdea Integrated Hlth Org, Dept Traumatol, San Sebastian, Spain
Univ Basque Country UPV EHU, Dept Nusing 2, San Sebastian 20014, Spain
Hernández-Laín, A:
Hosp Univ 12 Octubre, Dept Neuropathol, Madrid 28041, Spain
Inst Invest Sanitaria Hosp 12 Octubre imas12, Madrid 28041, Spain
Complutense Univ Madrid UCM, Fac Med, Dept Pathol, Madrid 28040, Spain
Domínguez-González, C:
Ctr Biomed Network Res Rare Dis CIBERER, Carlos Hlth Inst 3, Spanish Minist Sci & Innovat, Madrid 28029, Spain
Inst Invest Sanitaria Hosp 12 Octubre imas12, Madrid 28041, Spain
Hosp 12 Octubre, Dept Neurol, Neuromuscular Unit, Madrid 28041, Spain
Vílchez, JJ:
Ctr Biomed Network Res Rare Dis CIBERER, Carlos Hlth Inst 3, Spanish Minist Sci & Innovat, Madrid 28029, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Hosp Univ & Politecn La Fe, Neurol Dept, Neuromuscular Dis Unit, Valencia, Spain
Iruzubieta, P:
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Biogipuzkoa Hlth Res Inst, RNA Biol & Therapies Grp, Neurogenet, Neurosci Area, San Sebastian 20014, Spain
McGill Univ, Montreal Neurol Hosp & Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
de Munain, AL:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Univ Donostia, Osakidetza, Dept Neurol, E-20014 San Sebastian, Guipuzcoa, Spain
Univ Basque Country UPV EHU, Dept Neurosci, San Sebastian 20014, Spain
Univ Deusto, Fac Med, Bilbao 48007, Spain
Sáenz, A:
Biogipuzkoa Hlth Res Inst, Neuromuscular Dis Grp, Neurosci Area, San Sebastian 20014, Spain
Spanish Natl Hlth Inst Carlos iii, Carlos Hlth Inst 3, CiberNed, Av Monforte de Lemos 3-5, Madrid 28029, Spain
Green Submitted, gold
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