Location of the axon initial segment assembly can be predicted from neuronal shape

Zhuang Xu; Christopher N Angstmann; Yuhuang Wu; Holly Stefen; Esmeralda Parić; Thomas Fath; Paul M G Curmi

doi:10.1016/j.isci.2024.109264

Location of the axon initial segment assembly can be predicted from neuronal shape

iScience. 2024 Feb 17;27(3):109264. doi: 10.1016/j.isci.2024.109264. eCollection 2024 Mar 15.

Authors

Zhuang Xu^{1

2

3}, Christopher N Angstmann³, Yuhuang Wu⁴, Holly Stefen⁵, Esmeralda Parić⁵, Thomas Fath⁵, Paul M G Curmi^{1

2}

Affiliations

¹ School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia.
² School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
³ School of Mathematics and Statistics, The University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Infection Analytics Program, Kirby Institute for Infection and Immunity, The University of New South Wales, Sydney, NSW 2052, Australia.
⁵ Dementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia.

Abstract

The axon initial segment (AIS) is located at the proximal axon demarcating the boundary between axonal and somatodendritic compartments. The AIS facilitates the generation of action potentials and maintenance of neuronal polarity. In this study, we show that the location of AIS assembly, as marked by Ankyrin G, corresponds to the nodal plane of the lowest-order harmonic of the Laplace-Beltrami operator solved over the neuronal shape. This correlation establishes a coupling between location of AIS assembly and neuronal cell morphology. We validate this correlation for neurons with atypical morphology and neurons containing multiple AnkG clusters on distinct neurites, where the nodal plane selects the appropriate axon showing enriched Tau. Based on our findings, we propose that Turing patterning systems are candidates for dynamically governing AIS location. Overall, this study highlights the importance of neuronal cell morphology in determining the precise localization of the AIS within the proximal axon.

Keywords: Cellular neuroscience; Classification Description: Molecular neuroscience.