Modeling protein-protein interactions in axon initial segment to understand their potential impact on action potential initiation

Piyush Bhardwaj; Don Kulasiri; Sandhya Samarasinghe

doi:10.4103/1673-5374.295332

Modeling protein-protein interactions in axon initial segment to understand their potential impact on action potential initiation

Neural Regen Res. 2021 Apr;16(4):700-706. doi: 10.4103/1673-5374.295332.

Authors

Piyush Bhardwaj¹, Don Kulasiri¹, Sandhya Samarasinghe²

Affiliations

¹ Centre of Advanced Computational Solutions (C-fACS); Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
² Centre of Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand.

Abstract

The axon initial segment (AIS) region is crucial for action potential initiation due to the presence of high-density AIS protein voltage-gated sodium channels (Na_v). Na_v channels comprise several serine residues responsible for the recruitment of Na_v channels into the structure of AIS through interactions with ankyrin-G (AnkG). In this study, a series of computational experiments are performed to understand the role of AIS proteins casein kinase 2 and AnkG on Na_v channel recruitment into the AIS. The computational simulation results using Virtual cell software indicate that Na_v channels with all serine sites available for phosphorylation bind to AnkG with strong affinity. At the low initial concentration of AnkG and casein kinase 2, the concentration of Na_v channels reduces significantly, suggesting the importance of casein kinase 2 and AnkG in the recruitment of Na_v channels.

Keywords: Alzheimer’s disease; ankyrin-G; axon initial segment; casein kinase-2; microtubules; voltage-gated potassium channel; voltage-gated sodium channel.