Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner
Abstract Sarcoglycanopathies are heterogeneous proximo-distal diseases presenting severe muscle alterations. Although there are 6 different sarcoglycan isoforms, sarcoglycanopathies are caused exclusively by mutations in genes coding for one of the four sarcoglycan transmembrane proteins (alpha, bet...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07353-1 |
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| author | Michela Gloriani Bianca Cheli Chiara D’Ercole Veronica Ruggieri Marianna Cosentino Mireia Serrat Pineda Biliana Lozanoska-Ochser Francesca Grassi Marina Bouché Luca Madaro Carles Sánchez Riera |
| author_facet | Michela Gloriani Bianca Cheli Chiara D’Ercole Veronica Ruggieri Marianna Cosentino Mireia Serrat Pineda Biliana Lozanoska-Ochser Francesca Grassi Marina Bouché Luca Madaro Carles Sánchez Riera |
| author_sort | Michela Gloriani |
| collection | DOAJ |
| description | Abstract Sarcoglycanopathies are heterogeneous proximo-distal diseases presenting severe muscle alterations. Although there are 6 different sarcoglycan isoforms, sarcoglycanopathies are caused exclusively by mutations in genes coding for one of the four sarcoglycan transmembrane proteins (alpha, beta, gamma and delta) forming the sarcoglycan complex (SGC) in skeletal and cardiac muscle. Little is known about the different roles of the SGC beyond the dystrophin glycoprotein complex (DGC) structural role. Here, we show that SGC proteins are enriched at the post-synaptic membrane of neuromuscular junctions (NMJs). Using a mouse model lacking the beta-sarcoglycan subunit, we describe for the first time that the loss of the SGC in the NMJ area results in alterations of pre- and postsynaptic membrane, as well as a significant reduction of membrane potential. Moreover, using different denervated wild-type mouse models, we demonstrate that nerve presence precedes the sarcoglycan enrichment at NMJ, suggesting a nerve-dependent sarcoglycan expression. Altogether, our findings suggest that pathological decline should no longer be understood only in terms of sarcolemma damage but also in terms of sarcoglycans’ participation in the NMJ. Henceforth, our work paves the way for the identification of new mechanisms involving sarcoglycans and new approaches for the treatment of sarcoglycanopathies. |
| format | Article |
| id | doaj-art-3b4fbb81ed70412c8df1021b0d408da6 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-3b4fbb81ed70412c8df1021b0d408da62025-01-26T12:54:45ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111110.1038/s41419-025-07353-1Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent mannerMichela Gloriani0Bianca Cheli1Chiara D’Ercole2Veronica Ruggieri3Marianna Cosentino4Mireia Serrat Pineda5Biliana Lozanoska-Ochser6Francesca Grassi7Marina Bouché8Luca Madaro9Carles Sánchez Riera10Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeSorbonne Université, INSERM UMRS 974, Association Institut de Myologie, Centre de recherche en MyologieDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of RomeAbstract Sarcoglycanopathies are heterogeneous proximo-distal diseases presenting severe muscle alterations. Although there are 6 different sarcoglycan isoforms, sarcoglycanopathies are caused exclusively by mutations in genes coding for one of the four sarcoglycan transmembrane proteins (alpha, beta, gamma and delta) forming the sarcoglycan complex (SGC) in skeletal and cardiac muscle. Little is known about the different roles of the SGC beyond the dystrophin glycoprotein complex (DGC) structural role. Here, we show that SGC proteins are enriched at the post-synaptic membrane of neuromuscular junctions (NMJs). Using a mouse model lacking the beta-sarcoglycan subunit, we describe for the first time that the loss of the SGC in the NMJ area results in alterations of pre- and postsynaptic membrane, as well as a significant reduction of membrane potential. Moreover, using different denervated wild-type mouse models, we demonstrate that nerve presence precedes the sarcoglycan enrichment at NMJ, suggesting a nerve-dependent sarcoglycan expression. Altogether, our findings suggest that pathological decline should no longer be understood only in terms of sarcolemma damage but also in terms of sarcoglycans’ participation in the NMJ. Henceforth, our work paves the way for the identification of new mechanisms involving sarcoglycans and new approaches for the treatment of sarcoglycanopathies.https://doi.org/10.1038/s41419-025-07353-1 |
| spellingShingle | Michela Gloriani Bianca Cheli Chiara D’Ercole Veronica Ruggieri Marianna Cosentino Mireia Serrat Pineda Biliana Lozanoska-Ochser Francesca Grassi Marina Bouché Luca Madaro Carles Sánchez Riera Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner Cell Death and Disease |
| title | Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner |
| title_full | Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner |
| title_fullStr | Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner |
| title_full_unstemmed | Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner |
| title_short | Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner |
| title_sort | sarcoglycans are enriched at the neuromuscular junction in a nerve dependent manner |
| url | https://doi.org/10.1038/s41419-025-07353-1 |
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