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Front Mol Neurosci. 2018 Sep 4;11:319. doi: 10.3389/fnmol.2018.00319. eCollection 2018.

The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling.

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Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, University of Porto, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal.


In the adult nervous system axon caliber varies widely amongst different tracts. When considering a given axon, its diameter can further fluctuate in space and time, according to processes including the distribution of organelles and activity-dependent mechanisms. In addition, evidence is emerging supporting that in axons circumferential tension/contractility is present. Axonal diameter is generically regarded as being regulated by neurofilaments. When neurofilaments are absent or low, microtubule-dependent mechanisms can also contribute to the regulation of axon caliber. Despite this knowledge, the fine-tune mechanisms controlling diameter and circumferential tension throughout the lifetime of an axon, remain largely elusive. Recent data supports the role of the actin-spectrin-based membrane periodic skeleton and of non-muscle myosin II in the control of axon diameter. However, the cytoskeletal arrangement that underlies circumferential axonal contraction and expansion is still to be discovered. Here, we discuss in a critical viewpoint the existing knowledge on the regulation of axon diameter, with a specific focus on the possible role played by the axonal actin cytoskeleton.


axon diameter; axonal contractility; axonal cytoskeleton; axonal tension; membrane periodic skeleton

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