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

Lalli G, Schiavo G - J. Cell Biol. (2002)

Bottom Line: However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular NeuroPathoBiology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.

ABSTRACT
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.

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TeNT HC carriers and Lysotracker-positive organelles show distinct motile properties. (a) Relative frequency of speed values observed between two consecutive frames (interval = 5 s) for TeNT HC carriers (n = 364 vesicles, black bars) and Lysotracker-containing organelles (n = 235 vesicles, gray bars). Retrograde movement is conventionally shown as positive. (b) The incidence of reversal (number of changes of direction per organelle) for Lysotracker-positive vesicles is 11 times higher than TeNT HC carriers.
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fig4: TeNT HC carriers and Lysotracker-positive organelles show distinct motile properties. (a) Relative frequency of speed values observed between two consecutive frames (interval = 5 s) for TeNT HC carriers (n = 364 vesicles, black bars) and Lysotracker-containing organelles (n = 235 vesicles, gray bars). Retrograde movement is conventionally shown as positive. (b) The incidence of reversal (number of changes of direction per organelle) for Lysotracker-positive vesicles is 11 times higher than TeNT HC carriers.

Mentions: A comparison of the motile behavior displayed by TeNT HC– and the Lysotracker-positive organelles further demonstrates that they are distinct compartments (Fig. 4) . The speed distribution for TeNT HC carriers extends to values of >3 μm/s and is retrogradely biased, whereas the organelles stained by Lysotracker are slower and display a higher frequency of anterograde movement (Fig. 4 a). Moreover, Lysotracker vesicles changed direction more frequently compared with TeNT HC organelles, as shown by the different incidence of reversal (Fig. 4 b). These observations demonstrate that TeNT HC follows an axonal retrograde route able to bypass lysosomal targeting.


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

Lalli G, Schiavo G - J. Cell Biol. (2002)

TeNT HC carriers and Lysotracker-positive organelles show distinct motile properties. (a) Relative frequency of speed values observed between two consecutive frames (interval = 5 s) for TeNT HC carriers (n = 364 vesicles, black bars) and Lysotracker-containing organelles (n = 235 vesicles, gray bars). Retrograde movement is conventionally shown as positive. (b) The incidence of reversal (number of changes of direction per organelle) for Lysotracker-positive vesicles is 11 times higher than TeNT HC carriers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199221&req=5

fig4: TeNT HC carriers and Lysotracker-positive organelles show distinct motile properties. (a) Relative frequency of speed values observed between two consecutive frames (interval = 5 s) for TeNT HC carriers (n = 364 vesicles, black bars) and Lysotracker-containing organelles (n = 235 vesicles, gray bars). Retrograde movement is conventionally shown as positive. (b) The incidence of reversal (number of changes of direction per organelle) for Lysotracker-positive vesicles is 11 times higher than TeNT HC carriers.
Mentions: A comparison of the motile behavior displayed by TeNT HC– and the Lysotracker-positive organelles further demonstrates that they are distinct compartments (Fig. 4) . The speed distribution for TeNT HC carriers extends to values of >3 μm/s and is retrogradely biased, whereas the organelles stained by Lysotracker are slower and display a higher frequency of anterograde movement (Fig. 4 a). Moreover, Lysotracker vesicles changed direction more frequently compared with TeNT HC organelles, as shown by the different incidence of reversal (Fig. 4 b). These observations demonstrate that TeNT HC follows an axonal retrograde route able to bypass lysosomal targeting.

Bottom Line: However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular NeuroPathoBiology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus