title: Surface expression and subunit specific control of steady protein levels by the Kv7.2 helix A-B linker.
abstract: Kv7.2 and Kv7.3 are the main components of the neuronal voltage-dependent M-current, which is a subthreshold potassium conductance that exerts an important control on neuronal excitability. Despite their predominantly intracellular distribution, these channels must reach the plasma membrane in order to control neuronal activity. Thus, we analyzed the amino acid sequence of Kv7.2 to identify intrinsic signals that may control its surface expression. Removal of the interlinker connecting helix A and helix B of the intracellular C-terminus produces a large increase in the number of functional channels at the plasma membrane. Moreover, elimination of this linker increased the steady-state amount of protein, which was not associated with a decrease of protein degradation. The magnitude of this increase was inversely correlated with the number of helix A - helix B linkers present in the tetrameric channel assemblies. In contrast to the remarkable effect on the amount of Kv7.2 protein, removal of the Kv7.2 linker had no detectable impact on the steady-state levels of Kv7.3 protein.
authors.affiliation: Unidad de Biofísica, CSIC, UPV/EHU, Universidad del País Vasco, Barrio Sarriena s/n, Leioa, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Aivar
authors.forename: Juncal
authors.initials: J
authors.lastname: Fernández-Orth
authors.forename: Carolina
authors.initials: C
authors.lastname: Gomis-Perez
authors.forename: Araitz
authors.initials: A
authors.lastname: Alberdi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Alaimo
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Rodríguez
authors.forename: Teresa
authors.initials: T
authors.lastname: Giraldez
authors.forename: Pablo
authors.initials: P
authors.lastname: Miranda
authors.forename: Pilar
authors.initials: P
authors.lastname: Areso
authors.forename: Alvaro
authors.initials: A
authors.lastname: Villarroel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D014981:Xenopus
chemical_list: D051658:KCNQ2 Potassium Channel