Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment.

Hanne B Rasmussen, Christian Frøkjaer-Jensen, Camilla Stampe Jensen, Henrik S Jensen, Nanna K Jørgensen, Hiroaki Misonou, James S Trimmer, Søren-Peter Olesen, Nicole Schmitt

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93 Citationer (Scopus)

Abstract

The potassium channel subunits KCNQ2 and KCNQ3 are believed to underlie the M current of hippocampal neurons. The M-type potassium current plays a key role in the regulation of neuronal excitability; however, the subcellular location of the ion channels underlying this regulation has been controversial. We report here that KCNQ2 and KCNQ3 subunits are localized to the axon initial segment of pyramidal neurons of adult rat hippocampus and in cultured hippocampal neurons. We demonstrate that the localization of the KCNQ2/3 channel complex to the axon initial segment is favored by co-expression of the two channel subunits. Deletion of the ankyrin-G-binding motif in both the KCNQ2 and KCNQ3 C-terminals leads to the disappearance of the complex from the axon initial segment, albeit the channel complex remains functional and still reaches the plasma membrane. We further show that although heteromeric assembly of the channel complex favours localization to the axon initial segment, deletion of the ankyrin-G-binding motif in KCNQ2 alone does not alter the subcellular localization of KCNQ2/3 heteromers. By contrast, deletion of the ankyrin-G-binding motif in KCNQ3 significantly reduces AIS enrichment of the complex, implicating KCNQ3 as a major determinant of M channel localization to the AIS.
Udgivelsesdato: 2007-Mar-15
OriginalsprogEngelsk
TidsskriftJournal of Cell Science
Vol/bind120
Udgave nummerPt 6
Sider (fra-til)953-63
Antal sider10
ISSN0021-9533
DOI
StatusUdgivet - 2007

Bibliografisk note

Keywords: Amino Acid Motifs; Animals; Ankyrins; Axons; Binding Sites; COS Cells; Cell Membrane; Cells, Cultured; Cercopithecus aethiops; Female; Hippocampus; Ion Channel Gating; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Mutation; Neurons; Pregnancy; Protein Binding; Protein Subunits; Pyramidal Cells; Rats; Rats, Wistar

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