Slow axonal transport mechanisms move neurofilaments relentlessly in mouse optic axons.

Lasek, Raymond J.; Paggi, Paola; Katz, Michael J.

doi:10.1083/jcb.117.3.607

Cited by 84 publications

(75 citation statements)

References 54 publications

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“…The transport profiles were followed to 135 d after labeling and were interpreted as showing only progressive anterograde movement of the labeled proteins. Subsequent reports of slow axonal transport showed similar profiles demonstrating proximal to distal movement of cytoskeletal proteins (Ochs and Johnson, 1969;Griffin et al, 1978Griffin et al, , 1982Griffin et al, , 1984Lasek et al, 1992). These pulse-labeling experiments did not, however, preclude the existence of a retrograde slow component.…”

Section: Discussionmentioning

confidence: 62%

Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves

Glass

Griffin

1994

J. Neurosci.

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Slow axonal transport is the mechanism by which cytoskeletal proteins are distributed within the axon. This function has traditionally been considered an exclusively unidirectional, anterograde process. Previous observations of cytoskeletal redistribution in surviving, transected axons of the C57BL/Ola mouse led us to hypothesize a retrograde component of cytoskeletal transport. To test this hypothesis against previous methods of measuring slow transport of cytoskeleton, we radioactively pulse-labeled proteins in sensory neurons of C57BL/Ola mice and followed their redistribution by gel fluorography in ligated and unligated sciatic nerves. Slow axonal transport of cytoskeletal proteins proceeded with the same characteristics in C57BL/Ola as in standard C57BL/6 mice. In comparison to the transport profiles from unligated control nerves, in ligated nerves there was redistribution of radiolabeled neurofilament and tubulin proteins back toward the cell body during the 14 d experimental period. These observations demonstrate that pulse-labeled cytoskeletal proteins move bidirectionally in this experimental system, and may provide insight into the normal mechanisms of cytoskeletal maintenance.

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Section: Discussionmentioning

confidence: 62%

Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves

Glass

Griffin

1994

J. Neurosci.

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“…F, Effect of varying k on and k off , keeping the ratio k on /k off constant (0.0013/0.021 ϭ 0.0619; 10,000 neurofilaments in the activated region). Lasek et al (1992) have argued that some faster-moving cytosolic proteins comigrate with neurofilament proteins by onedimensional SDS-PAGE, giving the appearance of two kinetic states for neurofilaments, when in fact there is only one. Using two-dimensional gels, these authors did not detect a distinct stationary component.…”

Section: Discussionmentioning

confidence: 99%

“…Long-term tracking of neurofilament protein transport in vivo on a time scale of days or weeks using radioisotopic pulse labeling has demonstrated that neurofilaments move slowly along axons in an anterograde direction at average rates of ϳ0.1-3 mm/d (i.e., 0.001-0.03 m/s) (Nixon, 1991;Lasek et al, 1992). In contrast, short-term tracking of single neurofilaments in cultured neurons on a time scale of seconds or minutes using live-cell fluorescence imaging has demonstrated that these cytoskeletal polymers actually move at fast rates, which average ϳ0.4 -0.6 m/s, and that their movements are both bidirectional and intermittent (Roy et al, 2000;Wang et al, 2000;Wang and Brown, 2001;Ackerley et al, 2003;Uchida and Brown, 2004).…”

Section: Introductionmentioning

confidence: 99%

Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons

Trivedi

Jung²,

Brown³

2007

J. Neurosci.

139

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We have developed a novel pulse-escape fluorescence photoactivation technique to investigate the long-term pausing behavior of axonal neurofilaments. Cultured sympathetic neurons expressing a photoactivatable green fluorescent neurofilament fusion protein were illuminated with violet light in a short segment of axon to create a pulse of fluorescent neurofilaments. Neurofilaments departed from the photoactivated regions at rapid velocities, but the overall loss of fluorescence was slow because many of the neurofilaments paused for long periods of time before moving. The frequency of neurofilament departure was more rapid initially and slower at later times, resulting in biphasic decay kinetics. By computational simulation of the kinetics, we show that the neurofilaments switched between two distinct states: a mobile state characterized by intermittent movements and short pauses (average ϭ 30 s) and a stationary state characterized by remarkably long pauses (average ϭ 60 min). On average, the neurofilaments spent 92% of their time in the stationary state. Combining short and long pauses, they paused for 97% of the time, resulting in an average transport rate of 0.5 mm/d. We speculate that the relative proportion of the time that neurofilaments spend in the stationary state may be a principal determinant of their transport rate and distribution along axons, and a potential target of mechanisms that lead to abnormal neurofilament accumulations in disease.

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“…Another possibility is that phosphorylation alters the proportion of neurofilaments that are undergoing proximodistal transport. Whether most neurofilament organelles are moving (Lasek et al, 1992) or most are stationary has been a controversial issue (for reviews, see Hollenbeck, 1989;Lasek et al, 1992;Ochs and Brimijoin, 1993). Several lines of evidence suggest that there is a substantial stationary cytoskeleton (Nixon and Logvinenko, 1986;Nixon et al, 1987;Hollenbeck, 1989;Nixon and Sihag, 1991), and that phosphorylated neurofilaments are closely associated with the stationary phase (Watson et al, 1989a(Watson et al, , 1991.…”

Section: Effects Of Myelination On Neurojilament Numbermentioning

confidence: 99%

Regional modulation of neurofilament organization by myelination in normal axons

et al. 1994

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Previous studies in the hypomyelinating mouse mutant Trembler have suggested that demyelinating axons are smaller in caliber compared to normal axons, and that there are differences in the organization of axonal neurofilaments. In the normal PNS, however, the relationship between neurofilament organization and myelination has not been investigated extensively. In normal axons, only the initial segments, the nodes of Ranvier (approximately 1 micron), and the terminals are not covered by myelin. We took advantage of an unusual feature of the primary sensory neurons in the dorsal root ganglion, the relatively long nonmyelinated stem process (up to several hundred micrometers), to determine if the presence of myelination correlates with differences in cytoskeletal organization and neurofilament phosphorylation. Axonal caliber and neurofilament numbers were substantially greater in the myelinated internodes than in the stem process or nodes of Ranvier. Neurofilament spacing, assessed by measuring the nearest-neighbor neurofilament distance, was 25–50% less in the stem processes and nodes of Ranvier than in the myelinated internodes. In the myelinated internodes, neurofilaments had greater immunoreactivity for phosphorylated epitopes than those in the stem process. These findings indicate that interactions with Schwann cells modulate neurofilament phosphorylation within the ensheathed axonal segments, and that increased phosphorylation within myelinated internodes leads to greater interfilament spacing. Lastly, the myelinated internodes had three fold more neurofilaments, but the same number of microtubules. Both the increased neurofilament spacing and the increase in neurofilament numbers in myelinated internodes contribute to a greater axonal caliber in the myelinated internodes.

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Slow axonal transport mechanisms move neurofilaments relentlessly in mouse optic axons.

Abstract: Abstract. Pulse-labeling studies of slow axonal trans-

Cited by 84 publications

References 54 publications

Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves

Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves

Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons

Regional modulation of neurofilament organization by myelination in normal axons

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