Calcineurin Signaling Mediates Disruption of the Axon Initial Segment Cytoskeleton after Injury.

ABSTRACT: The axon initial segment (AIS) cytoskeleton undergoes rapid and irreversible disruption prior to cell death after injury, and loss of AIS integrity can produce profound neurological effects on the nervous system. Here we described a previously unrecognized mechanism for ischemia-induced alterations in AIS integrity. We show that in hippocampal CA1 pyramidal neurons Na_v1.6 mostly preserves at the AIS after disruption of the cytoskeleton in a mouse model of middle cerebral artery occlusion. Genetic removal of neurofascin-186 leads to rapid disruption of Na_v1.6 following injury, indicating that neurofascin is required for Na_v1.6 maintenance at the AIS after cytoskeleton collapse. Importantly, calcineurin inhibition with FK506 fully protects AIS integrity and s

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC7031317 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature