Submit to Biomolecules Review for Biomolecules Propose a Special Issue

Journal Browser

► Journal Browser

The Neuromuscular Junction in Health and Disease

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15560

Share This Special Issue

Special Issue Editors

Dr. Lucia Tabares

E-Mail Website
Guest Editor

Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain
Interests: synapse; exocytosis; endocytosis; neuromuscular junction; neurotransmission; spinal muscular atrophy; synaptic proteins; mitochondria

Dr. Saravanan Arumugam

E-Mail
Co-Guest Editor

Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain
Interests: spinal muscular atrophy; neurodegeneration; motor neurons; hyperexcitability; NMJ; RNA methylation

Special Issue Information

Spinal motor neurons use a very specialized synapse, the neuromuscular junction (NMJ), to drive skeletal muscle movements. Our knowledge of the NMJ’s structure and function has been the basis for understanding chemical synapses in the nervous system. Due to its large size and experimental accessibility in many organism models, the NMJ can be studied at different stages, from embryonic to adulthood. Advances in genetic, molecular biology, and super-resolution microscopy techniques have allowed us to address new aspects of the NMJ’s molecular organization and regulation in health and disease. Of increasing interest are, for example, the interplay between the synaptic nanomachines (i.e., synaptic vesicles, mitochondria, endosomes, active zones, and the cytoskeleton), the function of the pre- and postsynaptic adhesion proteins, the dialog and interdependence between the pre- and postsynaptic elements, and the regulatory mechanisms for synaptic protein expression and function during development, maturation, and aging. Moreover, we are starting to better understand the electrophysiological and morphological deficits in this synapse that produce neuromuscular transmission disorders ranging from congenital myasthenic syndromes (CMSs) to Lambert–Eaton Syndrome and Spinal Muscular Atrophy.

This Special Issue aims to summarize our current understanding of the most important and novel aspects of the NMJ's physiology and pathophysiology.

Prof. Lucia Tabares
Dr. Saravanan Arumugam
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

synaptic proteins
synaptopathies
exocytosis
neurotransmitter secretion
myasthenic syndromes
spinal muscular atrophy

Published Papers (4 papers)

Download All Papers

Research

Jump to: Review

15 pages, 3881 KiB

Open AccessCommunication

Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons

by Cristina Pinto, Viviana Pérez, Jessica Mella, Miguel Albistur, Teresa Caprile, Francisca C. Bronfman and Juan Pablo Henríquez

Biomolecules 2021, 11(12), 1898; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11121898 - 17 Dec 2021

Cited by 4 | Viewed by 2628

Abstract

The vertebrate neuromuscular junction (NMJ) is formed by a presynaptic motor nerve terminal and a postsynaptic muscle specialization. Cumulative evidence reveals that Wnt ligands secreted by the nerve terminal control crucial steps of NMJ synaptogenesis. For instance, the Wnt3 ligand is expressed by motor neurons at the time of NMJ formation and induces postsynaptic differentiation in recently formed muscle fibers. However, the behavior of presynaptic-derived Wnt ligands at the vertebrate NMJ has not been deeply analyzed. Here, we conducted overexpression experiments to study the expression, distribution, secretion, and function of Wnt3 by transfection of the motor neuron-like NSC-34 cell line and by in ovo electroporation of chick motor neurons. Our findings reveal that Wnt3 is transported along motor axons in vivo following a vesicular-like pattern and reaches the NMJ area. In vitro, we found that endogenous Wnt3 expression increases as the differentiation of NSC-34 cells proceeds. Although NSC-34 cells overexpressing Wnt3 do not modify their morphological differentiation towards a neuronal phenotype, they effectively induce acetylcholine receptor clustering on co-cultured myotubes. These findings support the notion that presynaptic Wnt3 is transported and secreted by motor neurons to induce postsynaptic differentiation in nascent NMJs. Full article

(This article belongs to the Special Issue The Neuromuscular Junction in Health and Disease)

► Show Figures

Figure 1

27 pages, 8926 KiB

Open AccessArticle

Confocal Endomicroscopy of Neuromuscular Junctions Stained with Physiologically Inert Protein Fragments of Tetanus Toxin

by Cornelia Roesl, Elizabeth R. Evans, Kosala N. Dissanayake, Veronika Boczonadi, Ross A. Jones, Graeme R. Jordan, Leire Ledahawsky, Guy C. C. Allen, Molly Scott, Alanna Thomson, Thomas M. Wishart, David I. Hughes, Richard J. Mead, Clifford C. Shone, Clarke R. Slater, Thomas H. Gillingwater, Paul A. Skehel and Richard R. Ribchester

Biomolecules 2021, 11(10), 1499; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11101499 - 12 Oct 2021

Viewed by 2389

Abstract

Live imaging of neuromuscular junctions (NMJs) in situ has been constrained by the suitability of ligands for inert vital staining of motor nerve terminals. Here, we constructed several truncated derivatives of the tetanus toxin C-fragment (TetC) fused with Emerald Fluorescent Protein (emGFP). Four constructs, namely full length emGFP-TetC (emGFP-865:TetC) or truncations comprising amino acids 1066–1315 (emGFP-1066:TetC), 1093–1315 (emGFP-1093:TetC) and 1109–1315 (emGFP-1109:TetC), produced selective, high-contrast staining of motor nerve terminals in rodent or human muscle explants. Isometric tension and intracellular recordings of endplate potentials from mouse muscles indicated that neither full-length nor truncated emGFP-TetC constructs significantly impaired NMJ function or transmission. Motor nerve terminals stained with emGFP-TetC constructs were readily visualised in situ or in isolated preparations using fibre-optic confocal endomicroscopy (CEM). emGFP-TetC derivatives and CEM also visualised regenerated NMJs. Dual-waveband CEM imaging of preparations co-stained with fluorescent emGFP-TetC constructs and Alexa647-α-bungarotoxin resolved innervated from denervated NMJs in axotomized Wld^S mouse muscle and degenerating NMJs in transgenic SOD1G93A mouse muscle. Our findings highlight the region of the TetC fragment required for selective binding and visualisation of motor nerve terminals and show that fluorescent derivatives of TetC are suitable for in situ morphological and physiological characterisation of healthy, injured and diseased NMJs. Full article

(This article belongs to the Special Issue The Neuromuscular Junction in Health and Disease)

► Show Figures

Figure 1

Review

Jump to: Research

11 pages, 1733 KiB

Open AccessEditor’s ChoiceReview

Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States

by Scott P. Ginebaugh, Yomna Badawi, Tyler B. Tarr and Stephen D. Meriney

Biomolecules 2022, 12(6), 740; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12060740 - 24 May 2022

Cited by 3 | Viewed by 2438

Abstract

The mouse neuromuscular junction (NMJ) has long been used as a model synapse for the study of neurotransmission in both healthy and disease states of the NMJ. Neurotransmission from these neuromuscular nerve terminals occurs at highly organized structures called active zones (AZs). Within AZs, the relationships between the voltage-gated calcium channels and docked synaptic vesicles govern the probability of acetylcholine release during single action potentials, and the short-term plasticity characteristics during short, high frequency trains of action potentials. Understanding these relationships is important not only for healthy synapses, but also to better understand the pathophysiology of neuromuscular diseases. In particular, we are interested in Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disorder in which neurotransmitter release from the NMJ decreases, leading to severe muscle weakness. In LEMS, the reduced neurotransmission is traditionally thought to be caused by the antibody-mediated removal of presynaptic voltage-gated calcium channels. However, recent experimental data and AZ computer simulations have predicted that a disruption in the normally highly organized active zone structure, and perhaps autoantibodies to other presynaptic proteins, contribute significantly to pathological effects in the active zone and the characteristics of chemical transmitters. Full article

(This article belongs to the Special Issue The Neuromuscular Junction in Health and Disease)

► Show Figures

Figure 1

25 pages, 15651 KiB

Open AccessFeature PaperReview

by Kenji Takikawa and Hiroshi Nishimune

Biomolecules 2022, 12(2), 179; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12020179 - 21 Jan 2022

Cited by 5 | Viewed by 7290

Abstract

Synaptic transmission is essential for controlling motor functions and maintaining brain functions such as walking, breathing, cognition, learning, and memory. Neurotransmitter release is regulated by presynaptic molecules assembled in active zones of presynaptic terminals. The size of presynaptic terminals varies, but the size of a single active zone and the types of presynaptic molecules are highly conserved among neuromuscular junctions (NMJs) and central synapses. Three parameters play an important role in the determination of neurotransmitter release properties at NMJs and central excitatory/inhibitory synapses: the number of presynaptic molecular clusters, the protein families of the presynaptic molecules, and the distance between presynaptic molecules and voltage-gated calcium channels. In addition, dysfunction of presynaptic molecules causes clinical symptoms such as motor and cognitive decline in patients with various neurological disorders and during aging. This review focuses on the molecular mechanisms responsible for the functional similarities and differences between excitatory and inhibitory synapses in the peripheral and central nervous systems, and summarizes recent findings regarding presynaptic molecules assembled in the active zone. Furthermore, we discuss the relationship between functional alterations of presynaptic molecules and dysfunction of NMJs or central synapses in diseases and during aging. Full article

(This article belongs to the Special Issue The Neuromuscular Junction in Health and Disease)

► Show Figures