scholarly journals Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons

2003 ◽  
Vol 116 (22) ◽  
pp. 4639-4650 ◽  
Author(s):  
G. Lalli
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Retrograde Transport ◽  
Myosin Va

scholarly journals Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR

2002 ◽  
Vol 156 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Giovanna Lalli ◽  
Giampietro Schiavo
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Experimental System ◽  
Retrograde Transport ◽  
Endocytic Pathway ◽  
Neurotrophin Receptor ◽  
Tubular Structures ◽  
Growth And Survival ◽  
Membrane Compartments ◽  
The Central Nervous System

Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor neurons based on a fluorescent fragment of tetanus toxin (TeNT HC). Morphological and kinetic analysis of TeNT HC retrograde carriers reveals two major groups of organelles: round vesicles and fast tubular structures. TeNT HC carriers lack markers of the classical endocytic pathway and are not acidified during axonal transport. Importantly, TeNT HC and NGF share the same retrograde transport organelles, which are characterized by the presence of the neurotrophin receptor p75NTR. Our results provide the first direct visualization of retrograde transport in living motor neurons, and reveal a novel retrograde route that could be used both by physiological ligands (i.e., neurotrophins) and TeNT to enter the central nervous system.

scholarly journals New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Frances Theunissen ◽  
Phillip K. West ◽  
Samuel Brennan ◽  
Bojan Petrović ◽  
Kosar Hooshmand ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Retrograde Transport ◽  
Cytoskeletal Proteins ◽  
Charcot Marie Tooth Disease ◽  
Mitochondrial Homeostasis ◽  
Axonal Projections ◽  
Cytoskeletal Network ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective, early degeneration of motor neurons in the brain and spinal cord. Motor neurons have long axonal projections, which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability, anterograde and retrograde transport, and signaling between neurons. The formation of protein aggregates which contain cytoskeletal proteins, and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions, including ALS, Alzheimer's disease, Parkinson's disease, Huntington’s disease and Charcot-Marie-Tooth disease. Furthermore, it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately linked. Therefore, dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization, may be common pathways in the initial steps of neurodegeneration. Here we review and discuss known contributors, including variants in genetic loci and aberrant protein activities, which modify cytoskeletal integrity, axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative diseases. Additionally, we explore some emerging pathways that may contribute to this disruption in ALS.

Detoxified tetanus toxin (TETIM) – A superb nano-carrier for retro-axonal gene delivery to motor neurons in bypass of blood brain barriers

Toxicon ◽  
2019 ◽  
Vol 159 ◽  
pp. S12-S13
Author(s):  
Saak V. Ovsepian ◽  
MacDara Bodeker ◽  
Valerie B. O'Leary ◽  
J. Oliver Dolly
Keyword(s):  
Gene Delivery ◽  
Motor Neurons ◽  
Tetanus Toxin ◽  
Blood Brain ◽  
Brain Barriers

Retrograde transport and differential accumulation of serum proteins in motor neurons: Implications for motor neuron diseases

Neurology ◽  
1987 ◽  
Vol 37 (5) ◽  
pp. 843-843 ◽  
Author(s):  
T. Yamamoto ◽  
Y. Iwasaki ◽  
H. Konno ◽  
H. Iizuka ◽  
J.-X. Zhao
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Serum Proteins ◽  
Retrograde Transport ◽  
Motor Neuron Diseases

scholarly journals A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

2015 ◽  
Vol 83 (7) ◽  
pp. 2714-2724 ◽  
Author(s):  
Madison Zuverink ◽  
Chen Chen ◽  
Amanda Przedpelski ◽  
Faith C. Blum ◽  
Joseph T. Barbieri
Keyword(s):  
Motor Neurons ◽  
Disulfide Bond ◽  
Light Chain ◽  
Tetanus Toxin ◽  
Thioredoxin Reductase ◽  
Single Chain ◽  
Intact Cells ◽  
Spastic Paralysis ◽  
Interchain Disulfide Bond ◽  
N Terminus

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT) are the most potent toxins for humans and elicit unique pathologies due to their ability to traffic within motor neurons. BoNTs act locally within motor neurons to elicit flaccid paralysis, while retrograde TeNT traffics to inhibitory neurons within the central nervous system (CNS) to elicit spastic paralysis. BoNT and TeNT are dichain proteins linked by an interchain disulfide bond comprised of an N-terminal catalytic light chain (LC) and a C-terminal heavy chain (HC) that encodes an LC translocation domain (HCT) and a receptor-binding domain (HCR). LC translocation is the least understood property of toxin action, but it involves low pH, proteolysis, and an intact interchain disulfide bridge. Recently, Pirazzini et al. (FEBS Lett 587:150–155, 2013,http://dx.doi.org/10.1016/j.febslet.2012.11.007) observed that inhibitors of thioredoxin reductase (TrxR) blocked TeNT and BoNT action in cerebellar granular neurons. In the current study, an atoxic TeNT LC translocation reporter was engineered by fusing β-lactamase to the N terminus of TeNT [βlac-TeNT(RY)] to investigate LC translocation in primary cortical neurons and Neuro-2a cells. βlac-TeNT(RY) retained the interchain disulfide bond, showed ganglioside-dependent binding to neurons, required acidification to promote βlac translocation, and was sensitive to auranofin, an inhibitor of thioredoxin reductase. Mutation of βlac-TeNT(RY) at C439S and C467S eliminated the interchain disulfide bond and inhibited βlac translocation. These data support the requirement of an intact interchain disulfide for LC translocation and imply that disulfide reduction is a prerequisite for LC delivery into the host cytosol. The data also support a model that LC translocation proceeds from the C to the N terminus. βlac-TeNT(RY) is the first reporter system to measure translocation by an AB single-chain toxin in intact cells.

scholarly journals Selective binding, uptake, and retrograde transport of tetanus toxin by nerve terminals in the rat iris. An electron microscope study using colloidal gold as a tracer

1978 ◽  
Vol 77 (1) ◽  
pp. 1-13 ◽  
Author(s):  
ME Schwab ◽  
H Thoenen
Keyword(s):  
Electron Microscope ◽  
Tetanus Toxin ◽  
Colloidal Gold ◽  
Smooth Endoplasmic Reticulum ◽  
Specific Binding ◽  
Retrograde Transport ◽  
Nerve Terminals ◽  
Gold Complexes ◽  
Selective Binding ◽  
Gold Particles

A series of specific macromolecules (tetanus toxin, cholera toxin, nerve growth factor [NGF], and several lectins) have been shown to be transported retrogradely with high selectivity from terminals to cell bodies in various types of neurons. Under identical experimental conditions (low protein concentrations injected), most other macromolecules, e.g. horseradish peroxidase (HRP), albumin, ferritin, are not transported in detectable amounts. In the present EM study, we demonstrate selective binding of tetanus toxin to the surface membrane of nerve terminals, followed by uptake and subsequent retorgrade axonal transport. Tetanus toxin or albumin was adsorbed to colloidal gold particles (diam 200 A). The complex was shown to be stable and well suited as an EM tracer. 1-4 h after injection into the anterior eye chamber of adult rats, tetanus toxin-gold particles were found to be selectively associated with membranes of nerve terminals and preterminal axons. Inside terminals and axons, the tracer was localized mainly in smooth endoplasmic reticulum (SER)-like membrane compartments. In contrast, association of albumin-gold complexes with nervous structures was never observed, in spite of extensive uptake into fibroblasts. Electron microscope and biochemical experiments showed selective retrograde transport of tetanus toxin-gold complexes to the superior cervical ganglion. Specific binding to membrane components at nerve terminals and subsequent internalization and retrograde transport may represent an important pathway for macromolecules carrying information from target organs to the perikarya of their innervating neurons.

Immunization does not interfere with uptake and transport by motor neurons of the binding fragment of tetanus toxin

2006 ◽  
Vol 83 (8) ◽  
pp. 1540-1543 ◽  
Author(s):  
Paul S. Fishman ◽  
Christopher C. Matthews ◽  
Deborah A. Parks ◽  
Michael Box ◽  
Neil F. Fairweather
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Uptake And Transport
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