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Updated: Oct 29, 2025

Use of Primary Cultured Hippocampal Neurons to Study the Assembly of Axon Initial Segments
Published on: February 12, 2021
Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral
Elise Lv Malavasi1, Aniket Ghosh1, Daniel G Booth2
1Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Abstract:
Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells, and fusion of heminodes results in the establishment of nodes. Here we show that assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. The neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes, thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.
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