title: Calmodulin regulates the trafficking of KCNQ2 potassium channels.
abstract: Voltage-dependent potassium KCNQ2 (Kv7.2) channels play a prominent role in the control of neuronal excitability. These channels must associate with calmodulin to function correctly and, indeed, a mutation (R353G) that impairs this association provokes the onset of a form of human neonatal epilepsy known as benign familial neonatal convulsions (BFNC). We show here that perturbation of calmodulin binding leads to endoplasmic reticulum (ER) retention of KCNQ2, reducing the number of channels that reach the plasma membrane. Interestingly, elevating the expression of calmodulin in the BFNC mutant partially restores the intracellular distribution of the KCNQ channel. In contrast, overexpression of a Ca(2+)-binding incompetent calmodulin or sequestering of calmodulin promotes the retention of wild-type channels in the ER. Thus, a direct interaction with Ca(2+)-calmodulin appears to be critical for the correct activity of KCNQ2 potassium channels as it controls the channels' exit from the ER.
authors.affiliation: Unidad de Biofísica, CSIC-UPV/EHU, Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Etxeberria
authors.forename: Paloma
authors.initials: P
authors.lastname: Aivar
authors.forename: Jose Angel
authors.initials: JA
authors.lastname: Rodriguez-Alfaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Alaimo
authors.forename: Patricia
authors.initials: P
authors.lastname: Villacé
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Gómez-Posada
authors.forename: Pilar
authors.initials: P
authors.lastname: Areso
authors.forename: Alvaro
authors.initials: A
authors.lastname: Villarroel
mesh_terms: D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000378:metabolism; D009154:Mutation; D018408:Patch-Clamp Techniques; D021381:Protein Transport
chemical_list: D002147:Calmodulin; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D002118:Calcium