Review

The nano-architecture of the axonal cytoskeleton

  • Nature Reviews Neuroscience 18, 713726 (2017)
  • doi:10.1038/nrn.2017.129
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Abstract

The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton.

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Change history

  • Corrected online 16 November 2017

    In Box 1 of this article, the sentence "Actin filaments are approximately 8 nm in diameter, are composed of heterodimers of α-actin and β-actin (known as G-actin) and require ATP for polymerization" should have read "Actin filaments are approximately 8 nm in diameter, are composed of actin monomers (known as G-actin) and require ATP for polymerization". The article has been corrected in the online version.

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Acknowledgements

Work in the Leterrier laboratory is supported by the Centre National de la Recherche Scientifique (CNRS) Action Thématique et Incitative sur Programme (ATIP)–Avenir programme AO2016. Work in the Roy laboratory is supported by US National Institutes of Health (NIH) grants R01NS075233, R01AG048218 and R21 AG052404.

Author information

Affiliations

  1. NeuroCyto, Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN) Unités Mixtes de Recherche (UMR) 7259, Aix Marseille Université, Centre National de la Recherche Scientifique (CNRS), 3344 Cedex 15, Marseille, France.

    • Christophe Leterrier
  2. Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison.

    • Pankaj Dubey
    •  & Subhojit Roy
  3. Department of Neuroscience, University of Wisconsin–Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.

    • Subhojit Roy

Authors

  1. Search for Christophe Leterrier in:

  2. Search for Pankaj Dubey in:

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Contributions

C.L., P.D. and S.R. contributed to researching data for the article, making contributions to discussion of content and writing. C.L. and S.R. contributed equally to writing, reviewing and editing of the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christophe Leterrier or Subhojit Roy.

Glossary

Electron microscopy

A group of methods that generate an image of a sample by using a beam of electrons. Electrons can be detected after passing through the sample (transmission electron microscopy) or after being reflected (scanning electron microscopy). Electron microscopy can routinely reach 1 nm resolution (the size of a single amino acid) but usually requires the sample to be placed in a vacuum and is therefore destructive and most applicable to fixed samples labelled with specific procedures.

Immuno-electron microscopy

An electron microscopy modality in which proteins labelled by using antibodies that are tagged with small gold beads are imaged, allowing their localization.

Microtubule plus-end-tracking proteins

A set of proteins that bind the growing plus ends of microtubules. The core components of this complex are end-binding proteins, dimeric proteins that interact with the specific tubulin conformation found at the plus end.

Moiré effect

The emergence of a third pattern due to the superposition of two patterns with distinct frequencies. In microscopy, this effect is exploited in structured illumination microscopy by illuminating the sample with periodic patterns of light and using the resulting Moiré pattern to infer sample details that are beyond the diffraction limit.

Centrosome

An organelle that nucleates and controls the organization of microtubules and regulates cell-cycle progression.

Microtubule-associated proteins

(MAPs). The repertoire of proteins that bind to microtubules. They can associate with the microtubule lattice or with the minus end or plus end of the microtubules. Microtubule-associated molecular motor complexes are also MAPs.

Fluorescence recovery after photobleaching

A method used to measure the diffusion or transport of molecules. It requires tagging of the molecule of interest with a fluorescent marker, photobleaching of the label with a pulse of laser light and a subsequent measure of the rate of fluorescence recovery into the bleached area as other labelled molecules move into it.

Microfluidic

Of a method to manipulate cells (for seeding, incubation or labelling) at the sub-millimetre scale by using small volumes of medium that are pumped into miniaturized culturing devices.

En-passant boutons

Presynaptic specializations along axons that make contact with downstream neurons, as opposed to synaptic terminals at the extremity of axons. In hippocampal and cortical neuronal cultures, most presynapses are en-passant boutons.