Asymmetric turnover dynamics of Nav1.6 voltage-gated sodium channels at the axon initial segment

Authors

Yoshioka, D., Yamamoto, K., Huang, L., Abe, M., Sakimura, K., Kawai, T., Okochi, Y., Okamura, Y.

Abstract

Nav1.6 voltage-gated sodium channels are critical for shaping action potentials, and their precise localization at the axon initial segment (AIS) is essential for neuronal excitability. However, the turnover mechanisms that maintain this spatial pattern remain unclear. Here, we present a genetically engineered mouse in which endogenous Nav1.6 carries a Cre-switchable fluorescent tag, enabling us to simultaneously trace the turnover of pre-existing and newly synthesized Nav1.6 without perturbing AIS structure. Using this system, we determine the physiological lifetimes of Nav1.6 at the AIS in vivo and in vitro, and further uncover the spatially asymmetric turnover dynamics, with the proximal and distal AIS organizing a source-to-sink gradient. Based on the quantified parameters, computational modeling clarifies that this asymmetry promotes efficient clearance of older molecules, thereby supporting AIS quality control. Collectively, these findings provide a technical and conceptual foundation for understanding how molecular turnover contributes to AIS homeostasis.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 16 Sep 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.