Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Hee Jung Chung, Yuh Nung Jan, Lily Y. Jan

Research output: Contribution to journalArticle

Abstract

The M channels, important regulators of neuronal excitability, are voltage-gated potassium channels composed of KCNQ2-5 sub-units. Mutations in KCNQ2 and KCNQ3 cause benign familial neonatal convulsions (BFNC), dominantly inherited epilepsy and myokymia. Crucial for their functions in controlling neuronal excitability, the M channels must be placed at specific regions of the neuronal membrane. However, the precise distribution of surface KCNQ channels is not known. Here, we show that KCNQ2/KCNQ3 channels are preferentially localized to the surface of axons both at the axonal initial segment and more distally. Whereas axonal initial segment targeting of surface KCNQ channels is mediated by ankyrin-G binding motifs of KCNQ2 and KCNQ3, sequences mediating targeting to more distal portion of the axon reside in the membrane proximal and A domains of the KCNQ2 C-terminal tail. We further show that several BFNC mutations of KCNQ2 and KCNQ3 disrupt surface expression or polarized surface distribution of KCNQ channels, thereby revealing impaired targeting of KCNQ channels to axonal surfaces as a BFNC etiology.

Original languageEnglish (US)
Pages (from-to)8870-8875
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number23
DOIs
StatePublished - Jun 6 2006

Keywords

  • Axon initial segment
  • Axon targeting
  • Epilepsy
  • KCNQ potassium channel

ASJC Scopus subject areas

  • General

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