Episodic Ataxia Type-1 Mutations in the Kv1.1 Potassium Channel Display Distinct Folding and Intracellular Trafficking Properties

Episodic ataxia type 1 (EA-1) is a neurological disorder arising from mutations in the Kv1.1 potassium channel α-subunit. EA-1 patients exhibit substantial phenotypic variability resulting from at least 14 distinct EA-1 point mutations. We found that EA-1 missense mutations generate mutant Kv1.1 sub...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-12, Vol.276 (52), p.49427-49434
Main Authors: Manganas, Louis N., Akhtar, Sobia, Antonucci, Dana E., Campomanes, Claire R., Dolly, J. Oliver, Trimmer, James S.
Format: Article
Language:English
Subjects:
Animals
Ataxia - genetics
Ataxia - physiopathology
COS Cells
Humans
Kv1.1 Potassium Channel
Mutation
Neurons - physiology
Phenotype
Potassium Channels - chemistry
Potassium Channels - genetics
Potassium Channels - metabolism
Potassium Channels, Voltage-Gated
Protein Folding
Protein Transport - physiology
Rats
Ubiquitin - metabolism
Vimentin - metabolism
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Summary:Episodic ataxia type 1 (EA-1) is a neurological disorder arising from mutations in the Kv1.1 potassium channel α-subunit. EA-1 patients exhibit substantial phenotypic variability resulting from at least 14 distinct EA-1 point mutations. We found that EA-1 missense mutations generate mutant Kv1.1 subunits with folding and intracellular trafficking properties indistinguishable from wild-type Kv1.1. However, the single identified EA-1 nonsense mutation exhibits intracellular aggregation and detergent insolubility. This phenotype can be transferred to co-assembled Kv1 α- and Kvβ-subunits associated with Kv1.1 in neurons. These results suggest that as in many neurodegenerative disorders, intracellular aggregation of misfolded Kv1.1-containing channels may contribute to the pathophysiology of EA-1.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109325200