Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly de-stabilizing epileptogenic mutation-Reference-Cited by-同舟云学术

Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly de-stabilizing epileptogenic mutation

Published:2015-01-01 Issue: Volume: Page:
ISSN:1477-9137
Container-title:Journal of Cell Science
language:en
Short-container-title:

Author:

Alberdi Araitz¹,Gomis-Perez Carolina¹,Bernardo-Seisdedos Ganeko¹,Alaimo Alessandro¹,Malo Covadonga¹,Aldaregia Juncal¹,Lopez-Robles Carlos¹,Areso Pilar²,Butz Elisabeth³,Wahl-Schott Christian³,Villarroel Alvaro¹

Affiliation:

1. Unidad de Biofísica, Consejo Superior de Investigaciones Científicas, CSIC, UPV/EHU, Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Spain

2. Dept. Farmacología, UPV/EHU, Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Spain

3. Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität, 81377 München, Germany

Abstract

We show here that the combination of an intracellular bi-partite calmodulin (CaM) binding site and a distant assembly region affects how an ion channel is regulated by a membrane lipid. Our data reveal that regulation by phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) and stabilization of assembled Kv7.2 subunits by intracellular coiled-coil regions far from the membrane are coupled molecular processes. Live cell fluorescence energy transfer measurements and direct binding studies indicate that remote coiled-coil formation creates conditions for different CaM interaction modes, each conferring different PI(4,5)P2 dependency to Kv7.2 channels. Disruption of coiled-coil formation by an epilepsy causing mutation decreases apparent CaM binding affinity and interrupts CaM influence on PI(4,5)P2 sensitivity.

Publisher

The Company of Biologists

Subject

Cell Biology

Link

http://journals.biologists.com/jcs/article-pdf/128/21/4014/1940378/jcs176420.pdf

Reference63 articles.

1. Pharmacological inhibition of the M-current;Adams;J. Physiol.,1982

2. Surface expression and subunit specific control of steady protein levels by the kv7.2 helix A-B linker;Aivar;PLoS ONE,2012

3. Calmodulin activation limits the rate of KCNQ2 K+ channel exit from the endoplasmic reticulum;Alaimo;J. Biol. Chem.,2009

4. Cooperativity between calmodulin-binding sites in Kv7.2 channels;Alaimo;J. Cell Sci.,2013

5. The use of dansyl-calmodulin to study interactions with channels and other proteins;Alaimo;Methods Mol. Biol.,2013

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