Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels.

Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms.

The role of Src family kinases in egg activation.

The Src family kinases (SFKs) are believed to mediate some of the early events of egg activation at fertilization--intracellular Ca2+ increase and resumption of the second meiotic division (RMII). SFKs are both necessary and sufficient for triggering intracellular Ca2+ increase in eggs of sea urchin, sea star, Xenopus etc, but their role in mammalian eggs is not entirely determined. In this study we examined the involvement of SFKs in the events leading to Ca2+ increase in rat eggs and demonstrated their involvement in RMII.

Fibroblast growth factor homologous factors control neuronal excitability through modulation of voltage-gated sodium channels.

Neurons integrate and encode complex synaptic inputs into action potential outputs through a process termed "intrinsic excitability." Here, we report the essential contribution of fibroblast growth factor homologous factors (FHFs), a family of voltage-gated sodium channel binding proteins, to this process. Fhf1-/-Fhf4-/- mice suffer from severe ataxia and other neurological deficits.