1. Ankyrin-R Links Kv3.3 to the Spectrin Cytoskeleton and Is Required for Purkinje Neuron Survival.
- Author
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Stevens, Sharon R., van der Heijden, Meike E., Yuki Ogawa, Tao Lin, Sillitoe, Roy V., and Rasband, Matthew N.
- Subjects
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SPECTRIN , *CYTOSKELETAL proteins , *GRANULE cells , *CEREBELLAR nuclei , *SCAFFOLD proteins - Abstract
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 b3 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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