title: Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment.
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.
authors.affiliation: Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. hannebr@mfi.ku.dk
authors.forename: Hanne B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Christian
authors.initials: C
authors.lastname: Frøkjaer-Jensen
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Jensen
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Jensen
authors.forename: Nanna K
authors.initials: NK
authors.lastname: Jørgensen
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Misonou
authors.forename: James S
authors.initials: JS
authors.lastname: Trimmer
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitt
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001369:Axons / Q000502:physiology*; D001665:Binding Sites; D019556:COS Cells; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D006624:Hippocampus / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C490614:Ank3 protein, rat; D017487:Ankyrins; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; D021122:Protein Subunits