Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions
Desmin, the major intermediate filament (IF) protein in muscle cells, interlinks neighboring myofibrils and connects the whole myofibrillar apparatus to myonuclei, mitochondria, and the sarcolemma. However, desmin is also known to be enriched at postsynaptic membranes of neuromuscular junctions (NMJ...
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2020.567084/full |
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| author | Nane Eiber Franziska Fröb Mirjam Schowalter Christian Thiel Christian Thiel Christoph S. Clemen Christoph S. Clemen Christoph S. Clemen Rolf Schröder Rolf Schröder Said Hashemolhosseini Said Hashemolhosseini |
| author_facet | Nane Eiber Franziska Fröb Mirjam Schowalter Christian Thiel Christian Thiel Christoph S. Clemen Christoph S. Clemen Christoph S. Clemen Rolf Schröder Rolf Schröder Said Hashemolhosseini Said Hashemolhosseini |
| author_sort | Nane Eiber |
| collection | DOAJ |
| description | Desmin, the major intermediate filament (IF) protein in muscle cells, interlinks neighboring myofibrils and connects the whole myofibrillar apparatus to myonuclei, mitochondria, and the sarcolemma. However, desmin is also known to be enriched at postsynaptic membranes of neuromuscular junctions (NMJs). The pivotal role of the desmin IF cytoskeletal network is underscored by the fact that over 120 mutations of the human DES gene cause hereditary and sporadic myopathies and cardiomyopathies. A subgroup of human desminopathies comprises autosomal recessive cases resulting in the complete abolition of desmin protein. In these patients, who display a more severe phenotype than the autosomal dominant cases, it has been reported that some individuals also suffer from a myasthenic syndrome in addition to the classical occurrence of myopathy and cardiomyopathy. Since further studies on the NMJ pathology are hampered by the lack of available human striated muscle biopsy specimens, we exploited homozygous desmin knock-out mice which closely mirror the striated muscle pathology of human patients lacking desmin protein. Here, we report on the impact of the lack of desmin on the structure and function of NMJs and the transcription of genes coding for postsynaptic proteins. Desmin knock-out mice display a fragmentation of NMJs in soleus, but not in the extensor digitorum longus muscle. Moreover, soleus muscle fibers show larger NMJs. Further, transcription levels of acetylcholine receptor (AChR) genes are increased in muscles from desmin knock-out mice, especially of the AChRγ subunit, which is known as a marker of muscle fiber regeneration. Electrophysiological recordings depicted a pathological decrement of nerve-dependent endplate potentials and an increased rise time of the nerve-independent miniature endplate potentials. The latter appears related to the fragmentation of NMJs in desmin knockout mice. Our study highlights the essential role of desmin for the structural and functional integrity of mammalian NMJs. |
| first_indexed | 2024-12-10T09:41:20Z |
| format | Article |
| id | doaj.art-6017cf1596f149c0a79ffefa7a188735 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-10T09:41:20Z |
| publishDate | 2020-10-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-6017cf1596f149c0a79ffefa7a1887352022-12-22T01:53:59ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-10-011310.3389/fnmol.2020.567084567084Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular JunctionsNane Eiber0Franziska Fröb1Mirjam Schowalter2Christian Thiel3Christian Thiel4Christoph S. Clemen5Christoph S. Clemen6Christoph S. Clemen7Rolf Schröder8Rolf Schröder9Said Hashemolhosseini10Said Hashemolhosseini11Institute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyInstitute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyInstitute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyMedical Faculty, Institute of Human Genetics, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyMuscle Research Center Erlangen (MURCE), Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyInstitute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyInstitute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, GermanyMedical Faculty, Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, University of Cologne, Cologne, GermanyInstitute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyMuscle Research Center Erlangen (MURCE), Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyInstitute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyMuscle Research Center Erlangen (MURCE), Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyDesmin, the major intermediate filament (IF) protein in muscle cells, interlinks neighboring myofibrils and connects the whole myofibrillar apparatus to myonuclei, mitochondria, and the sarcolemma. However, desmin is also known to be enriched at postsynaptic membranes of neuromuscular junctions (NMJs). The pivotal role of the desmin IF cytoskeletal network is underscored by the fact that over 120 mutations of the human DES gene cause hereditary and sporadic myopathies and cardiomyopathies. A subgroup of human desminopathies comprises autosomal recessive cases resulting in the complete abolition of desmin protein. In these patients, who display a more severe phenotype than the autosomal dominant cases, it has been reported that some individuals also suffer from a myasthenic syndrome in addition to the classical occurrence of myopathy and cardiomyopathy. Since further studies on the NMJ pathology are hampered by the lack of available human striated muscle biopsy specimens, we exploited homozygous desmin knock-out mice which closely mirror the striated muscle pathology of human patients lacking desmin protein. Here, we report on the impact of the lack of desmin on the structure and function of NMJs and the transcription of genes coding for postsynaptic proteins. Desmin knock-out mice display a fragmentation of NMJs in soleus, but not in the extensor digitorum longus muscle. Moreover, soleus muscle fibers show larger NMJs. Further, transcription levels of acetylcholine receptor (AChR) genes are increased in muscles from desmin knock-out mice, especially of the AChRγ subunit, which is known as a marker of muscle fiber regeneration. Electrophysiological recordings depicted a pathological decrement of nerve-dependent endplate potentials and an increased rise time of the nerve-independent miniature endplate potentials. The latter appears related to the fragmentation of NMJs in desmin knockout mice. Our study highlights the essential role of desmin for the structural and functional integrity of mammalian NMJs.https://www.frontiersin.org/articles/10.3389/fnmol.2020.567084/fulldesminopathyskeletal muscleneuromuscular junctiondesminnicotinic acetylcholine receptorpostsynaptic gene |
| spellingShingle | Nane Eiber Franziska Fröb Mirjam Schowalter Christian Thiel Christian Thiel Christoph S. Clemen Christoph S. Clemen Christoph S. Clemen Rolf Schröder Rolf Schröder Said Hashemolhosseini Said Hashemolhosseini Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions Frontiers in Molecular Neuroscience desminopathy skeletal muscle neuromuscular junction desmin nicotinic acetylcholine receptor postsynaptic gene |
| title | Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions |
| title_full | Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions |
| title_fullStr | Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions |
| title_full_unstemmed | Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions |
| title_short | Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions |
| title_sort | lack of desmin in mice causes structural and functional disorders of neuromuscular junctions |
| topic | desminopathy skeletal muscle neuromuscular junction desmin nicotinic acetylcholine receptor postsynaptic gene |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2020.567084/full |
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