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

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

Research output: Contribution to journalArticle

74 Citations (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.

Original languageEnglish (US)
Pages (from-to)953-963
Number of pages11
JournalJournal of Cell Science
Volume120
Issue number6
DOIs
StatePublished - Mar 15 2007

Fingerprint

Ankyrins
KCNQ3 Potassium Channel
KCNQ2 Potassium Channel
Neurons
Pyramidal Cells
Ion Channels
Hippocampus
Potassium
Cell Membrane
Axon Initial Segment

Keywords

  • Ankyrin-G
  • Axon initial segment
  • Epilepsy
  • KCNQ
  • M current
  • Targeting

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rasmussen, H. B., Frøkjær-Jensen, C., Jensen, C. S., Jensen, H. S., Jørgensen, N. K., Misonou, H., ... Schmitt, N. (2007). Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment. Journal of Cell Science, 120(6), 953-963. https://doi.org/10.1242/jcs.03396

Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment. / Rasmussen, Hanne B.; Frøkjær-Jensen, Christian; Jensen, Camilla S.; Jensen, Henrik S.; Jørgensen, Nanna K.; Misonou, Hiroaki; Trimmer, James; Olesen, Søren Peter; Schmitt, Nicole.

In: Journal of Cell Science, Vol. 120, No. 6, 15.03.2007, p. 953-963.

Research output: Contribution to journalArticle

Rasmussen, HB, Frøkjær-Jensen, C, Jensen, CS, Jensen, HS, Jørgensen, NK, Misonou, H, Trimmer, J, Olesen, SP & Schmitt, N 2007, 'Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment', Journal of Cell Science, vol. 120, no. 6, pp. 953-963. https://doi.org/10.1242/jcs.03396
Rasmussen HB, Frøkjær-Jensen C, Jensen CS, Jensen HS, Jørgensen NK, Misonou H et al. Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment. Journal of Cell Science. 2007 Mar 15;120(6):953-963. https://doi.org/10.1242/jcs.03396
Rasmussen, Hanne B. ; Frøkjær-Jensen, Christian ; Jensen, Camilla S. ; Jensen, Henrik S. ; Jørgensen, Nanna K. ; Misonou, Hiroaki ; Trimmer, James ; Olesen, Søren Peter ; Schmitt, Nicole. / Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment. In: Journal of Cell Science. 2007 ; Vol. 120, No. 6. pp. 953-963.
@article{ec2bf7e79a334abbb010e88a949eece1,
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.",
keywords = "Ankyrin-G, Axon initial segment, Epilepsy, KCNQ, M current, Targeting",
author = "Rasmussen, {Hanne B.} and Christian Fr{\o}kj{\ae}r-Jensen and Jensen, {Camilla S.} and Jensen, {Henrik S.} and J{\o}rgensen, {Nanna K.} and Hiroaki Misonou and James Trimmer and Olesen, {S{\o}ren Peter} and Nicole Schmitt",
year = "2007",
month = "3",
day = "15",
doi = "10.1242/jcs.03396",
language = "English (US)",
volume = "120",
pages = "953--963",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "6",

}

TY - JOUR

T1 - Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment

AU - Rasmussen, Hanne B.

AU - Frøkjær-Jensen, Christian

AU - Jensen, Camilla S.

AU - Jensen, Henrik S.

AU - Jørgensen, Nanna K.

AU - Misonou, Hiroaki

AU - Trimmer, James

AU - Olesen, Søren Peter

AU - Schmitt, Nicole

PY - 2007/3/15

Y1 - 2007/3/15

N2 - 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.

AB - 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.

KW - Ankyrin-G

KW - Axon initial segment

KW - Epilepsy

KW - KCNQ

KW - M current

KW - Targeting

UR - http://www.scopus.com/inward/record.url?scp=34247372307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247372307&partnerID=8YFLogxK

U2 - 10.1242/jcs.03396

DO - 10.1242/jcs.03396

M3 - Article

C2 - 17311847

AN - SCOPUS:34247372307

VL - 120

SP - 953

EP - 963

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 6

ER -