Endocytosis and retrograde axonal traffic in motor neurons.

2005 ◽  
Vol 72 ◽  
pp. 139-150 ◽  
Author(s):  
Katrin Deinhardt ◽  
Giampietro Schiavo
Keyword(s):  
Spinal Cord ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Molecular Basis ◽  
Retrograde Transport ◽  
Membrane Dynamics ◽  
Transport Pathway ◽  
Precise Control ◽  
Recent Developments ◽  
Botulinum Neurotoxins

Spinal cord motor neurons control voluntary movement by relaying messages that arrive from upper brain centres to the innervated muscles. Despite the importance of motor neurons in human health and disease, the precise control of their membrane dynamics and its effect on motor neuron homoeostasis and survival are poorly understood. In particular, the molecular basis of the co-ordination of specific endocytic events with the axonal retrograde transport pathway is largely unknown. To study these important vesicular trafficking events, we pioneered the use of atoxic fragments of tetanus and botulinum neurotoxins to follow endocytosis and retrograde axonal transport in motor neurons. These neurotoxins bind specifically to pre-synaptic nerve terminals, where they are internalized. Whereas botulinum neurotoxins remain at the neuromuscular junction, tetanus toxin is retrogradely transported along the axon to the cell body, where it is released into the intersynaptic space and is internalized by adjacent inhibitory interneurons. The high neurospecificity and the differential intracellular sorting make tetanus and botulinum neurotoxins ideal tools to study neuronal physiology. In the present review, we discuss recent developments in our understanding of the internalization and trafficking of these molecules in spinal cord motor neurons. Furthermore, we describe the development of a reliable transfection method for motor neurons based on microinjection, which will be extremely useful for dissecting further the molecular basis of membrane dynamics and axonal transport in these cells.

Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons

2000 ◽  
Vol 7 (4) ◽  
pp. 274-285 ◽  
Author(s):  
Luc Dupuis ◽  
Marc de Tapia ◽  
Frédérique René ◽  
Bernadette Lutz-Bucher ◽  
Jon W. Gordon ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Transgenic Mice ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Differential Screening ◽  
Fast Axonal Transport ◽  
Transport Component

scholarly journals Role of MAP1B in axonal retrograde transport of mitochondria

2006 ◽  
Vol 397 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Eva-María Jiménez-Mateos ◽  
Christian González-Billault ◽  
Hana N. Dawson ◽  
Michael P. Vitek ◽  
Jesús Avila
Keyword(s):  
Axonal Transport ◽  
Retrograde Transport ◽  
Precise Control ◽  
Microtubule Associated Proteins ◽  
Anterograde Axonal Transport ◽  
Associated Proteins ◽  
Regulation Of Transport ◽  
The Stability ◽  
Additional Role

The MAPs (microtubule-associated proteins) MAP1B and tau are well known for binding to microtubules and stabilizing these structures. An additional role for MAPs has emerged recently where they appear to participate in the regulation of transport of cargos on the microtubules found in axons. In this role, tau has been associated with the regulation of anterograde axonal transport. We now report that MAP1B is associated with the regulation of retrograde axonal transport of mitochondria. This finding potentially provides precise control of axonal transport by MAPs at several levels: controlling the anterograde or retrograde direction of transport depending on the type of MAP involved, controlling the speed of transport and controlling the stability of the microtubule tracks upon which transport occurs.

scholarly journals Botulinum Neurotoxins A and E Undergo Retrograde Axonal Transport in Primary Motor Neurons

2012 ◽  
Vol 8 (12) ◽  
pp. e1003087 ◽  
Author(s):  
Laura Restani ◽  
Francesco Giribaldi ◽  
Maria Manich ◽  
Kinga Bercsenyi ◽  
Guillermo Menendez ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Motor Neurons ◽  
Retrograde Axonal Transport ◽  
Botulinum Neurotoxins

scholarly journals The Expression and Significance of Metallothioneins in Murine Organs and Tissues Following Mercury Vapour Exposure

2003 ◽  
Vol 31 (5) ◽  
pp. 514-523 ◽  
Author(s):  
Roger Kevin Stankovic ◽  
Victor Lee ◽  
Murat Kekic ◽  
Clive Harper
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Motor System ◽  
Grey Matter ◽  
Retrograde Transport ◽  
Ventral Root ◽  
Mercury Vapour ◽  
Wild Type ◽  
Double Knockout ◽  
The Central Nervous System

The fate of inspired mercury vapour (Hg0) is critical in the central nervous system (CNS) where it can circumvent the blood—brain barrier (BBB) at the neuromuscular junction (NMJ) and accumulate indefinitely in motor neurons by retrograde transport. The detoxification of systemic Hg0 by lung and liver requires investigation. We exposed 129/Sv wild-type (Wt) and 129/Sv MT-I, II double knockout (KO) mice to 500 μg Hg0/m3 for 4 hours to investigate the expression of MT in the lung, liver, and spinal cord following Hg0 exposure using unexposed groups as controls. There were congestive changes in liver and lung of both Wt and MT-KO groups of Hg0-treated mice; these changes appeared more pronounced in the MT-KO group. Motor neurons in the spinal cord did not show any pathological changes. Based on expression of MT, liver appears to have a major role in trapping and stabilising mercury. In the spinal cord, MT was expressed in all white matter astrocytes and in some grey matter astrocytes. Notably, motor neurons did not express MT, and the presence of MT could not be demonstrated in the axons of the ventral root. The absence of MT expression in motor neurons and their axons suggests the dependence of the motor system on the detoxifying capacity of liver MTs.

scholarly journals Changes in kinesin expression in the CNS of mice with dynein heavy chain 1 mutation.

2013 ◽  
Vol 60 (1) ◽  
Author(s):  
Magdalena Kuźma-Kozakiewicz ◽  
Beata Kaźmierczak ◽  
Ewa Usarek ◽  
Anna Barańczyk-Kuźma
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Heavy Chain ◽  
Clinical Symptoms ◽  
Retrograde Transport ◽  
Wild Type ◽  
Motor Neuron Degeneration ◽  
Anterograde Transport ◽  
A Minor ◽  
Minor Extent

Dysfunction of fast axonal transport, vital for motor neurons, may lead to neurodegeneration. Anterograde transport is mediated by N-kinesins (KIFs), while retrograde transport by dynein 1 and, to a minor extent, by C-kinesins. In our earlier studies we observed changes in expression of N- and C-kinesins (KIF5A, 5C, C2) in G93ASOD1-linked mouse model of motor neuron degeneration. In the present work we analyze the profile of expression of the same kinesins in mice with a dynein 1 heavy chain mutation (Dync1h1, called Cra1), presenting similar clinical symptoms, and in Cra1/SOD1 mice with milder disease progression than SOD1 transgenics. We found significantly higher levels of mRNA for KIF5A and KIF5C but not the KIFC2 in the frontal cortex of symptomatic Cra1/+ mice (aged 365 days) compared to the wild-type controls. No changes in kinesin expression were found in the spinal cord of any age group and only mild changes in the hippocampus. The expression of kinesins in the cerebellum of the presymptomatic and symptomatic mice (aged 140 and 365 days, respectively) was much lower than in age-matched controls. In Cra1/SOD1 mice the changes in KIFs expression were similar or more severe than in the Cra1/+ groups, and they also appeared in the spinal cord. Thus, in mice with the Dync1h1 mutation, which impairs dynein 1-dependent retrograde transport, expression of kinesin mRNA is affected in various structures of the CNS and the changes are similar or milder than in mice with double Dync1h1/hSOD1G93A mutations.

scholarly journals Receptor-Dependent and -Independent Axonal Retrograde Transport of Poliovirus in Motor Neurons

2009 ◽  
Vol 83 (10) ◽  
pp. 4995-5004 ◽  
Author(s):  
Seii Ohka ◽  
Mai Sakai ◽  
Stephanie Bohnert ◽  
Hiroko Igarashi ◽  
Katrin Deinhardt ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Retrograde Transport ◽  
Cytoplasmic Dynein ◽  
Dependent Manner ◽  
Fast Transport ◽  
Axonal Trafficking

ABSTRACT Poliovirus (PV), when injected intramuscularly into the calf, is incorporated into the sciatic nerve and causes an initial paralysis of the inoculated limb in transgenic (Tg) mice carrying the human PV receptor (hPVR/CD155) gene. We have previously demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerves of hPVR-Tg mice and that intramuscularly inoculated PV causes paralytic disease in an hPVR-dependent manner. Here we showed that hPVR-independent axonal transport of PV was observed in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Using primary motor neurons (MNs) isolated from these mice or rats, we demonstrated that the axonal transport of PV requires several kinetically different motor machineries and that fast transport relies on a system involving cytoplasmic dynein. Unexpectedly, the hPVR-independent axonal transport of PV was not observed in cultured MNs. Thus, PV transport machineries in cultured MNs and in vivo differ in their hPVR requirements. These results suggest that the axonal trafficking of PV is carried out by several distinct pathways and that MNs in culture and in the sciatic nerve in situ are intrinsically different in the uptake and axonal transport of PV.

Horseradish Peroxidase Studies in Animals with Neuromuscular Transpositions

1981 ◽  
Vol 90 (4) ◽  
pp. 396-397 ◽  
Author(s):  
G. David Neal ◽  
Dwight Sutton ◽  
Gregory Duncan ◽  
Charles W. Cummings
Keyword(s):  
Spinal Cord ◽  
Horseradish Peroxidase ◽  
Motor Neurons ◽  
Cervical Spinal Cord ◽  
Retrograde Transport ◽  
Laryngeal Nerve ◽  
Nucleus Ambiguus ◽  
Axonal Connections ◽  
Motor End Plate ◽  
Posterior Cricoarytenoid

Horseradish peroxidase (hrp) is used to trace axonal connections from the motor end-plate to the driving neuron. This technique has confirmed that the neurons activating the sternothyroid muscle are located in the cervical spinal cord, while those controlling the posterior cricoarytenoid (pca) are found in the nucleus ambiguus ipsilaterally. Eight rabbits underwent a sternothyroid ansa pedicle implantation to the pca at the time of sectioning the recurrent laryngeal nerve ipsilaterally. After two months, four of these animals received hrp injections into the previously implanted pca. Brainstem staining hrp did not reveal any retrograde transport to the motor neurons that were known to control the sternothyroid. Possible reasons for the failure of retrograde transport are discussed.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

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