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The Axonal Actin Filament Cytoskeleton: Structure, Function, and Relevance to Injury and Degeneration

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Abstract

Early investigations of the neuronal actin filament cytoskeleton gave rise to the notion that, although growth cones exhibit high levels of actin filaments, the axon shaft exhibits low levels of actin filaments. With the development of new tools and imaging techniques, the axonal actin filament cytoskeleton has undergone a renaissance and is now an active field of research. This article reviews the current state of knowledge about the actin cytoskeleton of the axon shaft. The best understood forms of actin filament organization along axons are axonal actin patches and a submembranous system of rings that endow the axon with protrusive competency and structural integrity, respectively. Additional forms of actin filament organization along the axon have also been described and their roles are being elucidated. Extracellular signals regulate the axonal actin filament cytoskeleton and our understanding of the signaling mechanisms involved is being elaborated. Finally, recent years have seen advances in our perspective on how the axonal actin cytoskeleton is impacted by, and contributes to, axon injury and degeneration. The work to date has opened new venues and future research will undoubtedly continue to provide a richer understanding of the axonal actin filament cytoskeleton.

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None available as this is a review article.

Abbreviations

ADF:

Actin depolymerizing factor

AIS:

Axon initial segment

AFB:

Actin filament bundles

ATP:

Adenosine triphosphate

BDNF:

Brain-derived neurotrophic factor

CSPGs:

Chondroitin sulfate proteoglycans

FMN2:

Formin-2

NGF:

Nerve growth factor

PI3K:

Phosphoinosite-3 kinase

PI(3,4,5)P3/PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

PTEN:

Phosphatase and tensin homolog

PMS:

Periodic membrane skeleton

ROCK:

RhoA-kinase

Sarm1:

Sterile alpha and TIR motif containing 1

Sema3A:

Semaphorin 3A

WAVE1:

WASP-family verpolin homologous protein 1

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Funding

This work was supported by NIH NINDS R56NS128049 to GG.

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Authors and Affiliations

  1. Department of Neural Sciences, Shriners Pediatric Research Center, Lewis Katz School of Medicine at Temple University, 3500 North Broad St, Philadelphia, PA, 19140, USA

    Gianluca Gallo

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GG wrote the manuscript, reviewed the literature, and prepared the figures.

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Correspondence to Gianluca Gallo.

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Highlights

The axonal actin cytoskeleton serves protrusive and contractile functions.

The axonal actin cytoskeleton forms a ring system to support the plasma membrane.

The axonal actin cytoskeleton protects from axon degeneration.

The axonal actin cytoskeleton is regulated by axonal endomembrane compartments.

The axonal actin cytoskeleton reorganizes during injury and degeneration.

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Gallo, G. The Axonal Actin Filament Cytoskeleton: Structure, Function, and Relevance to Injury and Degeneration. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-023-03879-7

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