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

Lalli, Giovanna; Gschmeissner, Steve; Schiavo, Giampietro

doi:10.1242/jcs.00727

Cited by 81 publications

(87 citation statements)

References 70 publications

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“…Thus, mutant SOD1 may sequester dynein within these aggregates, reducing the efficiency of dynein-mediated transport. In WT embryonic MNs, inhibition of dynein, which is critical for H C trafficking, reduces the fastest speed component of retrograde transport (30). A similar effect is found in SOD1 G93A mice in vivo (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…The speed distribution of retrograde carriers in cultured MNs was best described by the sum of speed components identified by Gaussian distributions centered at 0, 0.53, and 0.95 μm/s (details in Materials and Methods) (30). As expected by their speed distribution curve (Fig.…”

Section: Resultsmentioning

confidence: 67%

“…Purified H C was prepared as previously described (30) and labeled with AlexaFluor555-maleimide according to the manufacturer's instructions, followed by dialysis against PBS to remove unbound dye. TrkB and p75 NTR (27) antibodies were labeled with AlexaFluor555 using a monoclonal antibody labeling kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

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Deficits in axonal transport precede ALS symptoms in vivo

Bilsland¹,

Sahai

Kelly

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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343

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ALS is a fatal neurodegenerative disease characterized by selective motor neuron death resulting in muscle paralysis. Mutations in superoxide dismutase 1 (SOD1) are responsible for a subset of familial cases of ALS. Although evidence from transgenic mice expressing human mutant SOD1 G93A suggests that axonal transport defects may contribute to ALS pathogenesis, our understanding of how these relate to disease progression remains unclear. Using an in vivo assay that allows the characterization of axonal transport in single axons in the intact sciatic nerve, we have identified clear axonal transport deficits in presymptomatic mutant mice. An impairment of axonal retrograde transport may therefore represent one of the earliest axonal pathologies in SOD1 G93A mice, which worsens at an early symptomatic stage. A deficit in axonal transport may therefore be a key pathogenic event in ALS and an early disease indicator of motor neuron degeneration.

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Section: Discussionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 67%

See 1 more Smart Citation

Deficits in axonal transport precede ALS symptoms in vivo

Bilsland¹,

Sahai

Kelly

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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355

343

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“…For example, either EHNA or vanadate, which both inhibit dynein and other enzymes, inhibits axonal transport (Ekstrom and Kanje, 1984;Wang et al, 1995;Lalli et al, 2003). More specific dynein inhibition by genetic mutation causes changes in axonal organelle distributions consistent with transport defects (Bowman et al, 1999;Martin et al, 1999a;Koushika et al, 2004).…”

Section: Motors For Axonal Transport Of Mitochondriamentioning

confidence: 99%

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Pilling

Horiuchi

Lively

et al. 2006

MBoC

615

621

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To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150 Glued suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration. INTRODUCTIONOrganelle transport is central to the organization, developmental fate, and functions of asymmetric cells. A bipolar neuron is an extreme case, with the somato-dendritic region and the axon containing different sets of proteins and organelles. In general, much of the machinery for synthesizing and recycling neuronal components is clustered near the nucleus. Because an axon, often with an axial ratio of many thousands, usually contains Ͼ99% of the neuronal cytoplasm, active transport of new components away from the cell body and of spent components and trophic materials back toward the cell body is critical. Disruptions of axonal transport are thought to contribute to the pathologies of Alzheimer's, amyotrophic lateral sclerosis, and other neurodegenerative diseases (reviewed by Mandelkow and Mandelkow, 2002;Hirokawa and Takemura, 2005).Long-distance organelle transport in axons is driven by motor proteins that move along parallel microtubules whose plus ends are mostly oriented toward the axon terminal (reviewed by Hollenbeck and Saxton, 2005). There are multiple types of microtubule motors in postmitotic vertebrate neurons, including kinesins that can move toward either plus-or minus-ends and at least one cytoplasmic dynein that moves toward minus-ends (Martin et al., 1999b;Hirokawa and Takemura, 2005;Hollenbeck and Saxton, 2005). Which motors bind and move which axonal components? When multiple types of motors bind a single cargo, do they collaborate or compete, how are they regulated, and how do their combined activities generate an optimal distribution of that type of cargo?Axonal mitochondria are critical for the physiology of neurons and are particularly well suited for studying active tr...

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“…A number of studies have shown roles of MYO5 in neuronal transportation, exocytosis and synaptic plasticity 19 . For example, MYO5A transports endoplasmic reticulum vesicles 20 , secretory vesicles 21 , tetanus toxin 22 or mitochondria 23 in axons and mRNA/protein complex into dendritic spines 24 . Moreover, MYO5 controls exocytosis of large dense core vesicles 25 and the recycling of AMPA-type glutamate receptors to dendritic spines [26][27][28] .…”

mentioning

confidence: 99%

Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

Liu

Chen

et al. 2013

Nat Commun

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Polarized membrane addition is crucial for axon development and elongation during neuronal morphogenesis. This process is believed to be regulated by directed membrane trafficking of Rab10-containing post-Golgi carriers. However, the mechanisms underlying the biogenesis of these carriers remain unclear. Here, we report that Rab10 interaction with myosin Vb (MYO5B) determines the formation of Rab10 carriers and is important for axon development. Rab10 interacts with the exon D-encoded domain of MYO5B. Downregulating the expression of MYO5B ( þ D) or blocking its interaction with Rab10 impairs the fission of Rab10 vesicles from trans-Golgi membranes, causes a decrease in the number of Rab10 transport carriers and inhibits axon development in cultured hippocampal neurons. Furthermore, the MYO5B-Rab10 system is required for axon development of vertebrate neocortical neurons or zebrafish retinal ganglion cells in vivo. Thus, specific interaction between Rab10 and MYO5B controls the formation of Rab10 vesicles, which is required for axon development.

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

Cited by 81 publications

References 70 publications

Deficits in axonal transport precede ALS symptoms in vivo

Deficits in axonal transport precede ALS symptoms in vivo

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

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