Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation. 2015

Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
Unidad de BiofĂ­sica, Consejo Superior de Investigaciones CientĂ­ficas, CSIC, UPV/EHU, Barrio Sarriena s/n, Leioa 48940, Spain.

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.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D051658 KCNQ2 Potassium Channel A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS. KCNQ2 Protein,Kv7.2 Potassium Channel,Voltage-Gated K+ Channel KCNQ2,Potassium Channel, KCNQ2,Potassium Channel, Kv7.2,Voltage Gated K+ Channel KCNQ2
D019269 Phosphatidylinositol 4,5-Diphosphate A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994) PtdInsP2,Phosphatidylinositol 4,5-Biphosphate,Phosphatidylinositol Phosphate, PtdIns(4,5)P2,Phosphatidylinositol-4,5-Biphosphate,PtIns 4,5-P2,PtdIns(4,5)P2,PtdInsP,4,5-Biphosphate, Phosphatidylinositol,4,5-Diphosphate, Phosphatidylinositol,Phosphatidylinositol 4,5 Biphosphate,Phosphatidylinositol 4,5 Diphosphate

Related Publications

Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
March 2024, Biological chemistry,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
January 2017, Frontiers in molecular neuroscience,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
October 2017, Scientific reports,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
January 2014, Molecular and cellular neurosciences,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
January 2023, Advances in experimental medicine and biology,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
February 2023, The Journal of general physiology,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
May 2018, Biochimica et biophysica acta. Biomembranes,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
March 2023, International journal of molecular sciences,
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
January 2018, Channels (Austin, Tex.),
Araitz Alberdi, and Carolina Gomis-Perez, and Ganeko Bernardo-Seisdedos, and Alessandro Alaimo, and Covadonga Malo, and Juncal Aldaregia, and Carlos Lopez-Robles, and Pilar Areso, and Elisabeth Butz, and Christian Wahl-Schott, and Alvaro Villarroel
January 2006, Science's STKE : signal transduction knowledge environment,
Copied contents to your clipboard!