Episodic ataxia type-1 mutations in the Kv1.1 potassium channel display distinct folding and intracellular trafficking properties.

Abstract

Episodic ataxia type 1 (EA-1) is a neurological disorder arising from mutations in the Kv1.1 potassium channel alpha-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 alpha- and Kv beta-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.

• Authors: L N Manganas, S Akhtar, D E Antonucci, C R Campomanes, J O Dolly, J S Trimmer
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 52 Pg. 49427-34 (Dec 28 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11679591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• KCNA1 protein, human
• Potassium Channels
• Potassium Channels, Voltage-Gated
• Ubiquitin
• Vimentin
• Kv1.1 Potassium Channel

Topics

• Animals
• Ataxia (genetics, physiopathology)
• COS Cells
• Humans
• Kv1.1 Potassium Channel
• Mutation
• Neurons (physiology)
• Phenotype
• Potassium Channels (chemistry, genetics, metabolism)
• Potassium Channels, Voltage-Gated
• Protein Folding
• Protein Transport (physiology)
• Rats
• Ubiquitin (metabolism)
• Vimentin (metabolism)