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Updated: May 8, 2025

Visualizing Protein Kinase A Activity In Head-fixed Behaving Mice Using In Vivo Two-photon Fluorescence Lifetime Imaging Microscopy
Published on: June 7, 2019
ZNRF1-dependent regulation of AKT activity modulates Nav subcellular localization and AIS position in neurons to
Moeka Ohno1,2, Shuji Wakatsuki1, Hiroshi Kuniishi3
1Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
Abstract:
The axon initial segment (AIS) is a specialized compartment at the proximal axon, characterized by condensed localization of specific cytoskeletal proteins, including Ankyrin G (AnkG) and βIV-spectrin, which organize voltage-gated ion channels. The location and morphology of the AIS can change in response to neuronal activity; however, the precise mechanisms for the AIS plasticity remain unclear. Previously, we demonstrated that ubiquitin E3 ligase ZNRF1 is localized to presynaptic terminals in cultured hippocampal neurons and may play a role in Ca2+-dependent exocytosis. Here, we show that using ZNRF1 knockout (ZNRF1 KO) mice, ZNRF1-dependent AKT degradation induces AIS shift and increased cell surface localization of voltage-gated sodium channel Nav1.2. We also found that ZNRF1 KO mice exhibit enhanced short-term fear memory and increased contextual fear memory. These findings suggest that ZNRF1 may serve as a novel regulator of AIS localization.
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