The drebrin/EB3 pathway regulates cytoskeletal dynamics to drive neuritogenesis in embryonic cortical neurons

Poobalasingam, Thanushiyan; Bianco, Francesca; Oozeer, Fazal; Gordon‐Weeks, Phillip R.

doi:10.1111/jnc.15502

Cited by 7 publications

(11 citation statements)

References 52 publications

(109 reference statements)

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“…In this study, however, we did not find impaired elongation of axons in drebrin-knocked-down CX neurons, indicating that drebrin is dispensable for axon formation. It is possible that initial axon formation was actually delayed in drebrin-depleted neurons, as has been shown in cultured drebrin-knocked-out neurons 24 h after replating [4], but 2 days culture in our assay might have hidden the small difference between drebrin knockdown and the control. The dispensable role of drebrin in axon wiring is also shown in drebrin-knocked-out mice, in which no gross brain abnormalities have been found [32].…”

Section: Discussionmentioning

confidence: 92%

“…Therefore, drebrin can cross-link actin filaments and microtubules. Contribution of drebrin in actin filaments-microtubule interaction in neuronal process formation has been repeatedly shown [4, 8, 26, 27]. To compare the role of drebrin in elongating growth cones and leading-process growth cones, we knocked down drebrin in CX neurons and in MGE neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, drebrin can crosslink actin filaments and microtubules. Contribution of drebrin in actin filaments-microtubule interaction in neuronal process formation has been repeatedly shown [4,8,26,27] ing growth cones and leading-process growth cones, we knocked down drebrin in CX neurons and in MGE neurons. Almost complete knockdown of drebrin with the drebrin shRNA expression vector was proved by Western blotting (Fig.…”

Section: Inhibition Of Lamellipodia Formation and Drebrin Knockdownmentioning

confidence: 99%

“…Filopodia and lamellipodia play distinct role in the advance of the growth cone [3]. The filopodia detect guidance signals and support microtubule progression in the P domain [4]. Lamellipodia, on the other hand, show crawling behavior on the substrate.…”

Section: Introductionmentioning

confidence: 99%

“…There are many candidates that mediate the interaction between actin filaments and microtubules, including a recently focused actin-binding protein, drebrin [7]. Drebrin has been shown to be required for axonal growth [4] and for neuronal migration [8]. Accordingly, cytoskeletal machinery in growth cones can be classified into two systems: filopodia-drebrin-microtubule system and lamellipodia-drebrin-microtubule system.…”

Section: Introductionmentioning

confidence: 99%

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The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

Miyata

Hayashi²

2022

Dev Neurosci

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Neuronal migration and axon elongation in the developing brain are essential events for neural network formation. Leading processes of migrating neurons and elongating axons have growth cones at their tips. Cytoskeletal machinery for advance of growth cones of the two processes has been thought the same. In this study, we compared axonal elongating growth cones and leading process growth cones in the same conditions that manipulated filopodia, lamellipodia and drebrin, the latter mediates actin filament-microtubule interaction. Cerebral cortex (CX) neurons and medial ganglionic eminence (MGE) neurons from embryonic mice were cultured on less-adhesive cover glasses. Inhibition of filopodia formation by triple knock down of Mena, ENA and VASP or double knock down of Daam1 and fascin affected axon formation of CX neurons but did not affect the morphology of leading process of MGE neurons. On the other hand, treatment with CK666, to inhibit lamellipodia formation, did not affect axons, but destroyed the leading process growth cones. When drebrin was knocked down, the morphology of CX neurons remained unchanged, but the leading processes of MGE neurons became shorter. In vivo assay of radial migration of CX neurons revealed that drebrin knock down inhibited migration, while it did not affect axon elongation. These results showed that filopodia-microtubule system is the main driving machinery in elongating growth cones, while lamellipodia-drebrin-microtubule system is the main system in leading process growth cones of migrating neurons.

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Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Inhibition Of Lamellipodia Formation and Drebrin Knockdownmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

Miyata

Hayashi²

2022

Dev Neurosci

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SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model

Özer

Koyunoğlu

Son

et al. 2022

Molecular and Cellular Neuroscience

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Prolonged depletion of profilin 1 or F-actin causes an adaptive response in microtubules

Cisterna,

Skruber,

Jane

et al. 2024

Journal of Cell Biology

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In addition to its well-established role in actin assembly, profilin 1 (PFN1) has been shown to bind to tubulin and alter microtubule growth. However, whether PFN1’s predominant control over microtubules in cells occurs through direct regulation of tubulin or indirectly through the polymerization of actin has yet to be determined. Here, we manipulated PFN1 expression, actin filament assembly, and actomyosin contractility and showed that reducing any of these parameters for extended periods of time caused an adaptive response in the microtubule cytoskeleton, with the effect being significantly more pronounced in neuronal processes. All the observed changes to microtubules were reversible if actomyosin was restored, arguing that PFN1’s regulation of microtubules occurs principally through actin. Moreover, the cytoskeletal modifications resulting from PFN1 depletion in neuronal processes affected microtubule-based transport and mimicked phenotypes that are linked to neurodegenerative disease. This demonstrates how defects in actin can cause compensatory responses in other cytoskeleton components, which in turn significantly alter cellular function.

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The drebrin/EB3 pathway regulates cytoskeletal dynamics to drive neuritogenesis in embryonic cortical neurons

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 52 publications

The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model

Prolonged depletion of profilin 1 or F-actin causes an adaptive response in microtubules

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