Ion channel complexes promote action potential initiation at the mammalian axon initial segment (AIS), and modulation of AIS size by recruitment or loss of proteins can influence neuron excitability. Although endocytosis contributes to AIS turnover, how membrane proteins traffic to this proximal axonal domain is incompletely understood. Neurofascin186 (Nfasc186) has an essential role in stabilising the AIS complex to the proximal axon, and the AIS channel protein Kv7.3 regulates neuron excitability. Therefore, we have studied how these proteins reach the AIS. Vesicles transport Nfasc186 to the soma and axon terminal where they fuse with the neuronal plasma membrane. Nfasc186 is highly mobile after insertion in the axonal membrane and diffuses bidirectionally until immobilized at the AIS through its interaction with AnkyrinG. Kv7.3 is similarly recruited to the AIS. This study reveals how key proteins are delivered to the AIS and thereby how they may contribute to its functional plasticity.
- Aniket Ghosh
- Elise LV Malavasi
- Diane L Sherman
- Peter J Brophy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal work was performed according to UK legislation (Scientific Procedures) Act 1986 according to the guidelines of and approved by the University of Edinburgh Animal Welfare and Ethical Review Body. All work was performed under a Project Licence (No. P0F4A25E9 issued by the UK Home Office to Peter Brophy and this licence is in force until 26 March, 2022.
- Moses V Chao, New York University Langone Medical Center, United States
- Received: July 1, 2020
- Accepted: September 8, 2020
- Accepted Manuscript published: September 9, 2020 (version 1)
© 2020, Ghosh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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