論文

2021年11月16日

Ankyrin-R Links Kv3.3 to the Spectrin Cytoskeleton and Is Required for Purkinje Neuron Survival.

The Journal of neuroscience : the official journal of the Society for Neuroscience
  • Yuki Ogawa

記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1523/jneurosci.1132-21.2021, 10.1523/JNEUROSCI.1132-21.2021

Ankyrin scaffolding proteins are critical for membrane domain organization and protein stabilization in many different cell types including neurons. In the cerebellum, Ankyrin-R (AnkR) is highly enriched in Purkinje neurons, granule cells, and in the cerebellar nuclei (CN). Using male and female mice with a floxed allele for Ank1 in combination with Nestin-Cre and Pcp2-Cre mice, we found that ablation of AnkR from Purkinje neurons caused ataxia, regional and progressive neurodegeneration, and altered cerebellar output. We show that AnkR interacts with the cytoskeletal protein β3 spectrin and the potassium channel Kv3.3. Loss of AnkR reduced somatic membrane levels of β3 spectrin and Kv3.3 in Purkinje neurons. Thus, AnkR links Kv3.3 channels to the β3 spectrin-based cytoskeleton. Our results may help explain why mutations in β3 spectrin and Kv3.3 both cause spinocerebellar ataxia.SIGNIFICANCE STATEMENT Ankyrin scaffolding proteins localize and stabilize ion channels in the membrane by linking them to the spectrin-based cytoskeleton. Here, we show that Ankyrin-R (AnkR) links Kv3.3 K+ channels to the β3 spectrin-based cytoskeleton in Purkinje neurons. Loss of AnkR causes Purkinje neuron degeneration, altered cerebellar physiology, and ataxia, which is consistent with mutations in Kv3.3 and β3 spectrin causing spinocerebellar ataxia.

リンク情報
DOI
https://doi.org/10.1523/jneurosci.1132-21.2021
DOI
https://doi.org/10.1523/JNEUROSCI.1132-21.2021
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34785580
ID情報
  • DOI : 10.1523/jneurosci.1132-21.2021
  • DOI : 10.1523/JNEUROSCI.1132-21.2021
  • ORCIDのPut Code : 107660010
  • PubMed ID : 34785580

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