Referenced in: none

Automatically associated channels: Kv7.2

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

Authors: Araitz Alberdi, Carolina Gomis-Perez, Ganeko Bernardo-Seisdedos, Alessandro Alaimo, Covadonga Malo, Juncal Aldaregia, Carlos Lopez-Robles, Pilar Areso, Elisabeth Butz, Christian Wahl-Schott, Alvaro Villarroel

Journal, date & volume: J. Cell. Sci., 2015 Sep 10 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26359296

Abstract
We show that the combination of an intracellular bi-partite calmodulin (CaM)-binding site and a distant assembly region affect how an ion channel is regulated by a membrane lipid. Our data reveal that regulation by phosphatidylinositol(4,5)bisphosphate (PIP2) 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 PIP2 dependency to Kv7.2 channels. Disruption of coiled-coil formation by epilepsy-causing mutation decreases apparent CaM-binding affinity and interrupts CaM influence on PIP2 sensitivity.