Loss of Neurofascin-186 Disrupts Alignment of AnkyrinG Relative to Its Binding Partners in the Axon Initial Segment
Autor: | Arielle L. Baker, Michael B. Hoppa, Scott A Alpizar, Allan T. Gulledge |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Scaffold protein Hippocampal formation axon initial segment lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine neurofascin-186 ankyrin G medicine Axon lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Cell adhesion molecule Chemistry Sodium channel Axon initial segment Cell biology 030104 developmental biology medicine.anatomical_structure voltage gated sodium channels cultured hippocampal neurons 030217 neurology & neurosurgery Intracellular Function (biology) Neuroscience |
Zdroj: | Frontiers in Cellular Neuroscience, Vol 13 (2019) Frontiers in Cellular Neuroscience |
ISSN: | 1662-5102 |
Popis: | The axon initial segment (AIS) is a specialized region within the proximal portion of the axon that initiates action potentials thanks in large part to an enrichment of sodium channels. The scaffolding protein ankyrinG (AnkG) is essential for the recruitment of sodium channels as well as several other intracellular and extracellular proteins to the AIS. In the present study, we explore the role of the cell adhesion molecule (CAM) neurofascin-186 (NF-186) in arranging the individual molecular components of the AIS in cultured rat hippocampal neurons. Using a CRISPR depletion strategy to ablate NF expression, we found that the loss of NF selectively perturbed AnkG accumulation and its relative proximal distribution within the AIS. We found that the overexpression of sodium channels could restore AnkG accumulation, but not its altered distribution within the AIS without NF present. We go on to show that although the loss of NF altered AnkG distribution, sodium channel function within the AIS remained normal. Taken together, these results demonstrate that the regulation of AnkG and sodium channel accumulation within the AIS can occur independently of one another, potentially mediated by other binding partners such as NF. |
Databáze: | OpenAIRE |
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