WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience Advertisement
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, October 31, 2007, 27(44):12033-12044; doi:10.1523/JNEUROSCI.2282-07.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laezza, F.
Right arrow Articles by Nerbonne, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laezza, F.
Right arrow Articles by Nerbonne, J. M.

 Previous Article  |  Next Article 

Cellular/Molecular
The FGF14F145S Mutation Disrupts the Interaction of FGF14 with Voltage-Gated Na+ Channels and Impairs Neuronal Excitability

Fernanda Laezza,1,2 Benjamin R. Gerber,1 Jun-Yang Lou,1 Marie A. Kozel,1 Hali Hartman,3 Ann Marie Craig,2 David M. Ornitz,1 and Jeanne M. Nerbonne1

Departments of 1Molecular Biology and Pharmacology and 2Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri 63110, and 3Institute of Molecular Cardiology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201

Correspondence should be addressed to Dr. Jeanne M. Nerbonne, Department of Molecular Biology and Pharmacology, Box 8103, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110. Email: jnerbonne{at}wustl.edu

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming ({alpha}) subunits of voltage-gated Na+ (Nav) channels. The neurological phenotypes seen in Fgf14–/– mice and the identification of an FGF14 missense mutation (FGF14F145S) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14F145S reduces Nav {alpha} subunit expression at the axon initial segment, attenuates Nav channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14F145S does not interact directly with Nav channel {alpha} subunits. Rather, FGF14F145S associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Nav {alpha} subunits, suggesting that the mutant FGF14F145S protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Nav channel {alpha} subunits and altering neuronal excitability.

Key words: FHFs; Nav channels; action potentials; repetitive firing; axon initial segment; {alpha} subunit

Received May 18, 2007; revised Sept. 10, 2007; accepted Sept. 16, 2007.

Correspondence should be addressed to Dr. Jeanne M. Nerbonne, Department of Molecular Biology and Pharmacology, Box 8103, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110. Email: jnerbonne{at}wustl.edu






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-