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Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions

Eiber, N. and Fröb, F. and Schowalter, M. and Thiel, C. and Clemen, C.S. and Schröder, R. and Hashemolhosseini, S. (2020) Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions. Frontiers in Molecular Neuroscience, 13, p. 567084. Frontiers Media S.A.. doi: 10.3389/fnmol.2020.567084. ISSN 1662-5099.

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Official URL: https://www.frontiersin.org/articles/10.3389/fnmol.2020.567084/full

Abstract

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 AChRg 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.

Item URL in elib:https://elib.dlr.de/140152/
Document Type:Article
Title:Lack of Desmin in Mice Causes Structural and Functional Disorders of Neuromuscular Junctions
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Eiber, N.Institute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany,UNSPECIFIED
Fröb, F.Institute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany,UNSPECIFIED
Schowalter, M.Institute of Neuropathology, University Hospital Erlangen, FriedrichAlexander University Erlangen-Nurnberg, Erlangen, GermanyUNSPECIFIED
Thiel, C.Christian.Thiel (at) dlr.deUNSPECIFIED
Clemen, C.S.Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germanyhttps://orcid.org/0000-0002-1291-4219
Schröder, R.Institute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Bavaria, GermanyUNSPECIFIED
Hashemolhosseini, S.Institute of Biochemistry, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyUNSPECIFIED
Date:26 October 2020
Journal or Publication Title:Frontiers in Molecular Neuroscience
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:13
DOI :10.3389/fnmol.2020.567084
Page Range:p. 567084
Publisher:Frontiers Media S.A.
ISSN:1662-5099
Status:Published
Keywords:desminopathy, skeletal muscle, neuromuscular junction, desmin, nicotinic acetylcholine receptor, postsynaptic gene, myasthenic syndrome
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Systemphysiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Arndt, Carina
Deposited On:11 Jan 2021 13:26
Last Modified:11 Jan 2021 13:26

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