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Molecular Mechanisms of Neuromuscular Transmission in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 1983

Special Issue Editor


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Guest Editor
Institute of Integrative Neuroanatomy, Charité Medical School Berlin, 10115 Berlin, Germany
Interests: skeletal muscle; muscle physiology; excitation contraction coupling; exercise performance; neuromuscular signaling; neuromuscular physiology; contractile proteins; muscle proteins; skeletal muscle fibers; muscle damage; exercise; oxidative stress

Special Issue Information

Dear Colleagues,

At the postsynaptic neuromuscular junction, the molecular mechanisms converting the electrical impulses of nerve motors into the mechanical responses of the muscle remain to be fully understood.

While extensive studies have largely elucidated the molecular mechanisms at the presynaptic level of the neuromuscular junction, which regulate the axonal transport of neurotransmitters and their release into the synaptic cleft, little is known about the molecular mechanisms that regulate postsynaptic neuromuscular transmission, the signaling pathways involved, and their potential effect downstream of neurotransmitter receptors.

This Special Issue aims to bring together original molecular, biochemical and morphological studies mainly focusing on the molecular mechanisms affecting neuromuscular junction structure and the function of the skeletal muscle, both in healthy human and animal models and in various in vitro experimental models of muscle waste and myopathies.

Dr. Michele Salanova
Guest Editor

Manuscript Submission Information

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Keywords

  • neuromuscular junction
  • muscle atrophy
  • muscle postsynaptic signaling
  • muscle myopathy
  • NMJ in vitro models

Published Papers (1 paper)

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Research

21 pages, 3652 KiB  
Article
Opposite Regulation of Homer Signal at the NMJ Postsynaptic Micro Domain between Slow- and Fast-Twitch Muscles in an Experimentally Induced Autoimmune Myasthenia Gravis (EAMG) Mouse Model
by Martin Schubert, Andreas Pelz, Gabor Trautmann, Katharina Block, Sandra Furlan, Martina Gutsmann, Siegfried Kohler, Pompeo Volpe, Dieter Blottner, Andreas Meisel and Michele Salanova
Int. J. Mol. Sci. 2022, 23(23), 15052; https://doi.org/10.3390/ijms232315052 - 30 Nov 2022
Viewed by 1506
Abstract
Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and [...] Read more.
Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity. Soleus (SOL), extensor digitorum longus (EDL) and gastrocnemius (GAS) skeletal muscles are investigated. nAChR membrane clusters were studied to monitor neuromuscular junction (NMJ) integrity. Fibre-type cross-sectional area (CSA) analysis is carried out in order to determine the extent of muscle atrophy. Our findings clearly showed that crosslinking activity of Homer long forms (Homer 1b/c and Homer2a/b) are decreased in slow-twitch and increased in fast-twitch muscle of EAMG whereas the short form of Homer that disrupts Homer crosslinking (Homer1a) is upregulated in slow-twitch muscle only. Densitometry analysis showed a 125% increase in Homer protein expression in EDL, and a 45% decrease in SOL of EAMG mice. In contrast, nAChR fluorescence pixel intensity decreased in endplates of EAMG mice, more distinct in type-I dominant SOL muscle. Morphometric CSA of EAMG vs. control (CTR) revealed a significant reduction in EDL but not in GAS and SOL. Taken together, these results indicate that postsynaptic Homer signalling is impaired in slow-twitch SOL muscle from EAMG mice and provide compelling evidence suggesting a functional coupling between Homer and nAChR, underscoring the key role of Homer in skeletal muscle neurophysiology. Full article
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