Microtubule-based filopodium-like protrusions form after axotomy

Goldberg, Daniel J.; Burmeister, DW

doi:10.1523/jneurosci.12-12-04800.1992

Cited by 18 publications

(20 citation statements)

References 27 publications

(23 reference statements)

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“…However, many of the protrusions from these spines contain prominent EB3 label without detectable actin label (Fig. 6d, yellow arrowheads; supplemental Movie 8, available at www.jneurosci.org as supplemental material), indicating MTs may be capable of inducing tSHPs independently of actin polymerization, as has been demonstrated in axonal growth cones (Goldberg and Burmeister, 1992). Quantification of 47 tSHPs from the spine head shown in Figure 6d indicated that 55% (26 of 47) were MT-based without any accompanying actin polymerization, 19% (9 of 47) were MTbased with actin polymerization into the tSHP after MT polymer- ization, 9% (4 of 47) were formed by coincident MT and actin polymerization and 17% (8 of 47) were actin-based with no MT polymerization.…”

Section: Microtubules Remain Dynamic Throughout the Life Of The Neuronmentioning

confidence: 68%

Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines

Viesselmann²,

Nam³

et al. 2008

J. Neurosci.

264

291

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Dendritic spines are the primary sites of contact with presynaptic axons on excitatory hippocampal and cortical neurons. During development and plasticity spines undergo marked changes in structure that directly affect the functional communication between neurons. Elucidating the cytoskeletal events that induce these structural changes is fundamental to understanding synaptic biology. Actin plays a central role in the spine cytoskeleton, however the role of microtubules in spine function has been studied little. Although microtubules have a prominent role in transporting material throughout the dendrite that is destined for spines, they are not thought to directly influence spine structure or function. Using total internal reflectance fluorescent microscopy we discovered that microtubules rapidly invade dendritic protrusions of mature CNS neurons (up to 63 d in vitro), occasionally being associated with marked changes in spine morphology in the form of transient spine head protrusions (tSHPs). Two microtubules can occupy a spine simultaneously and microtubule targeting can occur from both the proximal and distal dendrite. A small percentage of spines are targeted at a time and all targeting events are transient, averaging only a few minutes. Nevertheless, over time many spines on a dendrite are targeted by microtubules. Importantly, we show that increasing neuronal activity enhances both the number of spines invaded by microtubules and the duration of these invasions. This study provides new insight into the dynamics of the neuronal cytoskeleton in mature CNS neurons and suggests that microtubules play an important, direct role in spine morphology and function.

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Section: Microtubules Remain Dynamic Throughout the Life Of The Neuronmentioning

confidence: 68%

Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines

Viesselmann²,

Nam³

et al. 2008

J. Neurosci.

264

291

View full text Add to dashboard Cite

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“…This concentration of nocodazole has no evident effect on fast axonal transport in the axon, as assessed by VEC-DIC microscopy, indicating it is insufficient to cause large-scale depolymerization of microtubules in the existing axon. It also does not decrease the formation of actin-based filopodia after axotomy (Goldberg and Burmeister, 1992).…”

Section: Resultsmentioning

confidence: 87%

“…from the end (Goldberg and Burmeister, 1992). Some of the filopodia that form are microtubulebased, and these can be eliminated by the use of nocodazole (Goldberg and Burmeister, 1992).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of formation of filopodia after axotomy by inhibitors of protein tyrosine kinases

Goldberg

1995

J. Neurobiol.

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The activity of motile protrusions of the growth cone--filopodia, veils, and lamellipodia--is essential for directed growth of a neuronal process. The regulation of the formation of these protrusions is not well understood. Numerous filopodia and veils or lamellipodia form within minutes of transection of an Aplysia axon in culture, as the initial components of growth cones of regenerating neurites. Axotomy, therefore, provides a robust and reliable protocol for analyzing the formation of these protrusions. We evaluated the involvement of protein phosphorylation in the regulation of protrusive activity. Of the inhibitors of protein kinases assayed, only the inhibitors of protein tyrosine kinases--genistein, lavendustin A, herbimycin A, and erbstatin analogue--suppressed the formation of protrusions, as assessed by high magnification video microscopy. These drugs did not work by preventing resealing of the axon, as evident from visual inspection and by the unimpaired effectiveness of genistein or lavendustin in preventing formation of filopodia when applied after resealing. Inhibition of protein tyrosine kinases not only prevented the formation of actin-based protrusions, but also caused deterioration of the actin network underlying the protrusive area of preexisting growth cones. Consistent with an involvement of protein tyrosine phosphorylation in the generation of protrusive structures, immunocytochemistry revealed that aggregates of phosphotyrosine appeared at the margins of the axon, from which protrusions emerge shortly after axotomy. These results suggest a role for protein tyrosine phosphorylation in the formation and maintenance of actin-based protrusive structures.

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“…Janson et al (2003) determined the polymerization of a single microtubule tip generates forces in the piconewton range. Goldberg and Burmeister (1992) demonstrated that microtubules produce sufficient force to generate protrusions from the severed ends of axons in the absence of actin filaments. Forces generated by microtubule tip polymerization may in turn be able to overcome intrinsic membrane tension and allow the axon to extend (Raucher and Sheetz, 2000).…”

Section: E14 Axon Extension In the Absence Of F-actin Requires Microtmentioning

confidence: 99%

Developmental regulation of sensory axon regeneration in the absence of growth cones

2006

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The actin filament (F-actin) cytoskeleton is thought to be required for normal axon extension during embryonic development. Whether this is true of axon regeneration in the mature nervous system is not known, but a progressive simplification of growth cones during development has been described and where specifically investigated, mature spinal cord axons appear to regenerate without growth cones. We have studied the cytoskeletal mechanisms of axon regeneration in developmentally early and late chicken sensory neurons, at embryonic day (E) 7 and 14 respectively. Depletion of F-actin blocked the regeneration of E7 but not E14 sensory axons in vitro. The differential sensitivity of axon regeneration to the loss of F-actin and growth cones correlated with endogenous levels of F-actin and growth cone morphology. The growth cones of E7 axons contained more F-actin and were more elaborate than those of E14 axons. The ability of E14 axons to regenerate in the absence of F-actin and growth cones was dependent on microtubule tip polymerization. Importantly, while the regeneration of E7 axons was strictly dependent on F-actin, regeneration of E14 axons was more dependent on microtubule tip polymerization. Furthermore, E14 axons exhibited altered microtubule polymerization relative to E7, as determined by imaging of microtubule tip polymerization in living neurons. These data indicate that the mechanism of axon regeneration undergoes a developmental switch between E7 and E14 from strict dependence on F-actin to a greater dependence on microtubule polymerization. Collectively, these experiments indicate that microtubule polymerization may be a therapeutic target for promoting regeneration of mature neurons.

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Microtubule-based filopodium-like protrusions form after axotomy

Cited by 18 publications

References 27 publications

Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines

Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines

Inhibition of formation of filopodia after axotomy by inhibitors of protein tyrosine kinases

Developmental regulation of sensory axon regeneration in the absence of growth cones

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