title: FGF14 is a regulator of KCNQ2/3 channels.
abstract: KCNQ2/3 (Kv7.2/7.3) channels and voltage-gated sodium channels (VGSCs) are enriched in the axon initial segment (AIS) where they bind to ankyrin-G and coregulate membrane potential in central nervous system neurons. The molecular mechanisms supporting coordinated regulation of KCNQ and VGSCs and the cellular mechanisms governing KCNQ trafficking to the AIS are incompletely understood. Here, we show that fibroblast growth factor 14 (FGF14), previously described as a VGSC regulator, also affects KCNQ function and localization. FGF14 knockdown leads to a reduction of KCNQ2 in the AIS and a reduction in whole-cell KCNQ currents. FGF14 positively regulates KCNQ2/3 channels in a simplified expression system. FGF14 interacts with KCNQ2 at a site distinct from the FGF14-VGSC interaction surface, thus enabling the bridging of NaV1.6 and KCNQ2. These data implicate FGF14 as an organizer of channel localization in the AIS and provide insight into the coordination of KCNQ and VGSC conductances in the regulation of membrane potential.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.|Ion Channel Research Unit, Duke University Medical Center, Durham, NC 27710.
authors.forename: Juan Lorenzo
authors.initials: JL
authors.lastname: Pablo
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710; geoffrey.pitt@med.cornell.edu.|Ion Channel Research Unit, Duke University Medical Center, Durham, NC 27710.|Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Pitt
mesh_terms: D017487:Ankyrins / Q000378:metabolism; D000071040:Axon Initial Segment / Q000378:metabolism*; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D062557:NAV1.6 Voltage-Gated Sodium Channel; D034741:RNA, Small Interfering; C100681:SCN8A protein, human; D061566:Voltage-Gated Sodium Channels; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors
keywords: FGF14; KCNQ2; ankyrin-G; axon initial segment; fibroblast growth factor homologous factors