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FGF14 is a regulator of KCNQ2/3 channels.

TitleFGF14 is a regulator of KCNQ2/3 channels.
Publication TypeJournal Article
Year of Publication2017
AuthorsPablo JLorenzo, Pitt GS
JournalProc Natl Acad Sci U S A
Volume114
Issue1
Pagination154-159
Date Published2017 Jan 03
ISSN1091-6490
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.

DOI10.1073/pnas.1610158114
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27994149
PubMed Central IDPMC5224356