Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel

Durga P. Mohapatra, Dominic F. Siino, James Trimmer

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Voltage-gated potassium (Kv) channels comprise four transmembrane α subunits, often associated with cytoplasmic β subunits that impact channel expression and function. Here, we show that cell surface expression, voltage-dependent activation gating, and phosphorylation-dependent modulation of Kv2.1 are regulated by cytoplasmic N/C interaction within the α subunit. Kv2.1 surface expression is greatly reduced by C-terminal truncation. Tailless Kv2.1 channels exhibit altered voltage-dependent gating properties and lack the bulk of the phosphorylation-dependent modulation of channel gating. Remarkably, the soluble C terminus of Kv2.1 associates with tailless channels and rescues their expression, function, and phosphorylation-dependent modulation. Soluble N and C termini of Kv2.1 can also interact directly. We also show that the N/C-terminal interaction in Kv2.1 is governed by a 34 aa motif in the juxtamembrane cytoplasmic C terminus, and a 17 aa motif located in the N terminus at a position equivalent to the β subunit binding site in other Kv channels. Deletion of either motif disrupts N/C-terminal interaction and surface expression, function, and phosphorylation-dependent modulation of Kv2.1 channels. These findings provide novel insights into intrinsic mechanisms for the regulation of Kv2.1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles α/β subunit interaction in other Kv channels.

Original languageEnglish (US)
Pages (from-to)4982-4994
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number19
DOIs
StatePublished - May 7 2008

Keywords

  • Assembly
  • Electrophysiology
  • Hippocampal neurons
  • Immunocytochemistry
  • Phosphorylation
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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