Skip Navigation


Cardiovascular Research Advance Access first published online on April 5, 2008
This version [Corrected Proof] published online on April 25, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn085
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
79/3/427    most recent
cvn085v2
cvn085v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nicolas, C. S.
Right arrow Articles by Baró, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nicolas, C. S.
Right arrow Articles by Baró, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

IKs response to protein kinase A-dependent KCNQ1 phosphorylation requires direct interaction with microtubules

Céline S. Nicolas1,2,3, Kyu-Ho Park1,2,3,{dagger}, Aziza El Harchi1,2,3,{ddagger}, Jacques Camonis4, Robert S. Kass5, Denis Escande1,2,3, Jean Mérot1,2,3, Gildas Loussouarn1,2,3, Françoise Le Bouffant1,2,3 and Isabelle Baró1,2,3,*

1 Inserm, UMR915, l'institut du thorax, Nantes F-44035, France
2 CNRS, ERL3147, Nantes F-44035, France
3 Faculté de Médecine, Université de Nantes, Nantes F-44035, France
4 Inserm, U830, Institut Curie, Paris F-75248, France
5 Department of Pharmacology, Columbia University Medical Center, 630 West, 168th Street, New York, NY 10032, USA

* Corresponding author. Tel: +33 2 40 41 28 48; fax: +33 2 40 41 29 50. E-mail address: isabelle.baro{at}nantes.inserm.fr

Aims: KCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K+ channel responsible for IKs—a major repolarizing current in the human heart—and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known and undefined regulatory proteins. Thus, identification of proteins that modulate its biosynthesis, localization, activity, and/or degradation is of great interest from both a physiological and pathological point of view.

Methods and results: Using a yeast two-hybrid screening, we detected a direct interaction between β-tubulin and the KCNQ1 N-terminus. The interaction was confirmed by co-immunoprecipitation of β-tubulin and KCNQ1 in transfected COS-7 cells and in guinea pig cardiomyocytes. Using immunocytochemistry, we also found that they co-localized in cardiomyocytes. We tested the effects of microtubule-disrupting and -stabilizing agents (colchicine and taxol, respectively) on the KCNQ1–KCNE1 channel activity in COS-7 cells by means of the permeabilized-patch configuration of the patch-clamp technique. None of these agents altered IKs. In addition, colchicine did not modify the current response to osmotic challenge. On the other hand, the IKs response to protein kinase A (PKA)-mediated stimulation depended on microtubule polymerization in COS-7 cells and in cardiomyocytes. Strikingly, KCNQ1 channel and Yotiao phosphorylation by PKA—detected by phospho-specific antibodies—was maintained, as was the association of the two partners.

Conclusion: We propose that the KCNQ1–KCNE1 channel directly interacts with microtubules and that this interaction plays a major role in coupling PKA-dependent phosphorylation of KCNQ1 with IKs activation.

KEYWORDS K+ channel; Myocytes; PKA; Signal transduction; KCNQ1; β-tubulin

Time for primary review: 31 days

{dagger} Present address. IBBMC, Bâtiment 430, Université de Paris-Sud, F-91405 Orsay, France.

{ddagger} Present address. Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Circ. Res.Home page
G. Seebohm, N. Strutz-Seebohm, O. N. Ureche, U. Henrion, R. Baltaev, A. F. Mack, G. Korniychuk, K. Steinke, D. Tapken, A. Pfeufer, et al.
Long QT Syndrome-Associated Mutations in KCNQ1 and KCNE1 Subunits Disrupt Normal Endosomal Recycling of IKs Channels
Circ. Res., December 5, 2008; 103(12): 1451 - 1457.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.