Source: https://www.nature.com/articles/nrn.2017.129?error=cookies_not_supported&code=651588b5-f984-4deb-9d3c-9dbd71e69494
Timestamp: 2019-04-22 10:02:45+00:00

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Christophe Leterrier trained as an engineer, cell biologist and neuroscientist and recently established the NeuroCyto laboratory in Marseille, France. The laboratory is dedicated to the study of the organization, functions and dysfunction of the neuronal cytoskeleton by use of advanced microscopy techniques.
Pankaj Dubey received his Ph.D. from the Tata Institute of Fundamental Research, Mumbai, India, in 2016. During his Ph.D., he focused on the role of actin dynamics in spermatid release in Drosophila. As a postdoctoral researcher in the laboratory of Subhojit Roy at the University of Wisconsin–Madison, USA, he is exploring organization and function of various actin assemblies in mouse primary hippocampal neuronal cultures.
Subhojit Roy is a physician–scientist, cell biologist and neuropathologist and is interested in movement and transformation in biology — as it relates to physiological and pathological phenomena. The Roy laboratory is situated at the University of Wisconsin in Madison, USA, and current interests include the neuronal cytoskeleton and therapeutic approaches for neurodegenerative diseases.
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.
The unique morphology and function of axons are sustained by the organization of the key elements of their cytoskeleton: microtubules, neurofilaments and actin.
Classical methods (electron microscopy and biochemistry) have been critical in identifying the morphology and composition of axonal cytostructures.
More recently, super-resolution microscopy, live-cell imaging and other new optical methods have been applied to the study of the axonal cytoskeleton.
This has led to major discoveries, in particular the existence of axonal actin structures such as rings, hot spots, trails and patches.
This Review summarizes the latest advances in our understanding of the axonal cytoskeleton and discusses key open questions in this field, such as the functions of newly discovered structures and the interplay between different cytoskeletal components.
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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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.
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.
Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison.
Department of Neuroscience, University of Wisconsin–Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
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.
Correspondence to Christophe Leterrier or Subhojit Roy.
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.
An electron microscopy modality in which proteins labelled by using antibodies that are tagged with small gold beads are imaged, allowing their localization.
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.
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.
An organelle that nucleates and controls the organization of microtubules and regulates cell-cycle progression.
(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.
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.
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.
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.

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