FHFs resemble other fibroblast growth factors on a basis of amino acid composition and crystal structure but evolved to carry on distinct, FGF unrelated functions. To date, FHFs have been implicated most clearly in modulation of voltage gated sodium channels (VGSCs).
FHFs are the classical example of an increase in gene diversity through the alternative promoter usage and splicing. Hence, the multiplicity of isoforms makes this family of proteins an interesting yet, challenging research topic. Different isoforms of FHFs have distinct sub-cellular localizations and differently modulate voltage gated sodium channels. By influencing critical parameters of channel physiology, including voltage dependence of channel steady-state inactivation, recovery from inactivation and current density, the FHF family of proteins has emerged as important regulators of cellular excitability.
The role of different FHF isoforms in modulation of VGSCs and their influence on cellular excitability is the main topic of this thesis. Performed experiments aimed to: (i) establish a channel-binding surface, common to all FHFs, (ii) categorize major FHF isoforms into functional groups based on the ability to modulate sodium channel Nav1.6, (iii) elucidate the mechanism involved in A-type FHF induced long-term, use-dependent channel inactivation, and (iv) determine potential differential localization of A-type FHFs in the brain and in subcellular compartments of cerebellar, hippocampal and sensory neurons.
|Commitee:||Chappell, Richard, Kass, Robert, Krogh-Madson, Trine, Melendez-Vasquez, Carmen|
|School:||City University of New York|
|School Location:||United States -- New York|
|Source:||DAI-B 71/12, Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Physiology|
|Keywords:||Cellular excitability, Fibroblast, Fibroblast growth factor homologous factor (fhf), Growth factor, Proteins, Sodium channel inactivation, Voltage gated sodium channel|
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