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

Louis N. Manganas, Sobia Akhtar, Dana E. Antonucci, Claire R. Campomanes, J. Oliver Dolly, James Trimmer

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)49427-49434
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number52
DOIs
StatePublished - Dec 28 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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