The actin cytoskeleton in the axon of neurons

The cytoskeleton has to enable plasticity and function for several functional segments. The cytoskeleton of neurons consists of three major structures similar to the cytoskeleton of other eukaryote cells: A network of filamentous actin, microtubules, and neurofilaments [1]. The actin network represents a particularly interesting part, as its appearance changes between functional units of the neuronal cell. The actin-based cytoskeleton of the axon (while dendrites are numerous, neurons mostly only develop one axon [2]) resembles the respective functional subunit. 

The Axonal Initial Segment (AIS, [3]) at the beginning of the axon is marked by an increase in density of cytoskeletal proteins, such as actin, spectrins, ankyrin G and others. Next to action potential generation the function of this dense region is probably to regulate transport [4]. 

The plasticity of the axon along its length is established by a remarkable structure of a protein ensemble: The membrane-associated periodic neuronal cytoskeleton (MPS, [5]); a structure of periodic actin rings around the axonal tube. (figure3) 

Figure 3

 

 

This structure, first discovered with super-resolution imaging, is highly conserved in diverse types of neurons across species [6]. Actin is also present in other forms of structures along the axon: Axon trails and hotspot, implicated in transport [7] (figure2). 

The last functional unit of the axon represents the presynapse, which develops upon a contact site with a dendrite of another cell [8]. The substructure of the cytoskeleton of the presynapse changes again in respect to the axon shaft, due to the functional need of the presynapse [9]. 

While neurons can grow into large cells, the structure of the cytoskeleton, especially in the thin axons and synapses, is organized on a nanoscopic scale. Super-resolution has brought remarkable insights to the understanding of neuronal cell biology, such as the discovery of the MPS, specific organization between synapses (synaptic nano-columns, [10]) and actin sub-structures in the presynapse [11]. While we begin to pierce into the nanoscopic world of neuronal cell biology, many questions surrounding the functional organization and dynamics of processes in this extraordinary cell type remain unanswered. Pushing the understanding of the high functional diversity and dynamicity of the neuronal cell and its functional units, super-resolution imaging of the cytoskeleton is at the forefront of techniques for advanced neuroscience. Super-resolved observations of the neuronal cytoskeleton are brought to a larger scale with Abbelight’s ASTER illumination technique, that allows for a 150 µm x 150 µm field of view. With this unparalleled size of field of view for dSTORM, DNA-PAINT and PALM acquisitions, the Abbelight SAFE360 module enables to collect more data in one acquisition and allows to capture large cells such as neurons entirely. The spectral demixing option for multicolor acquisitions enables to capture an ensemble of up to three targets simultaneously without the need for aberration correction or prolonged acquisition time.  (figure1)

References

[1] R. B. Wuerker et J. B. Kirkpatrick, « Neuronal Microtubules, Neurofilaments, and Microfilaments », International Review of Cytology 33 (1972): 45‑75, https://doi.org/10.1016/s0074-7696(08)61448-5. 

[2] Anthony P. BARNES et Franck POLLEUX, « Establishment of Axon-Dendrite Polarity in Developing Neurons », Annual review of neuroscience 32 (2009): 347‑81, https://doi.org/10.1146/annurev.neuro.31.060407.125536. 

[3] S. L. Palay et al., « The Axon Hillock and the Initial Segment », The Journal of Cell Biology 38, no 1 (juillet 1968): 193‑201, https://doi.org/10.1083/jcb.38.1.193. 

[4] Christophe Leterrier et Bénédicte Dargent, « No Pasaran! Role of the Axon Initial Segment in the Regulation of Protein Transport and the Maintenance of Axonal Identity », Seminars in Cell & Developmental Biology 27 (mars 2014): 44‑51, https://doi.org/10.1016/j.semcdb.2013.11.001. 

[5] Ke Xu, Guisheng Zhong, et Xiaowei Zhuang, « Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons », Science 339, no 6118 (25 janvier 2013): 452‑56, https://doi.org/10.1126/science.1232251. 

[6] Jiang He et al., « Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species », Proceedings of the National Academy of Sciences 113, no 21 (24 mai 2016): 6029‑34, https://doi.org/10.1073/pnas.1605707113. 

[7] Archan Ganguly et al., « A dynamic formin-dependent deep F-actin network in axons », Journal of Cell Biology 210, no 3 (27 juillet 2015): 401‑17, https://doi.org/10.1083/jcb.201506110. 

[8] Thomas C. Südhof, « The cell biology of synapse formation », The Journal of cell biology 220, no 7 (2021), https://doi.org/10.1083/jcb.202103052. 

[9] Lorenzo A. Cingolani et Yukiko Goda, « Actin in Action: The Interplay between the Actin Cytoskeleton and Synaptic Efficacy », Nature Reviews. Neuroscience 9, no 5 (mai 2008): 344‑56, https://doi.org/10.1038/nrn2373. 

[10] Ai-Hui Hui Tang et al., « A trans-synaptic nanocolumn aligns neurotransmitter release to receptors », Nature 536, no 7615 (2016): 210‑14, https://doi.org/10.1038/nature19058. 

[11] Dominic Bingham et al., « Presynapses Contain Distinct Actin Nanostructures », The Journal of Cell Biology 222, no 10 (2 octobre 2023): e202208110, https://doi.org/10.1083/jcb.202208110. 

 

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