TY - JOUR T1 - Fibroblast Growth Factor Homologous Factor 2B: Association with Na<sub>v</sub>1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6765 LP - 6775 DO - 10.1523/JNEUROSCI.1628-04.2004 VL - 24 IS - 30 AU - Ellen K. Wittmack AU - Anthony M. Rush AU - Matthew J. Craner AU - Mitchell Goldfarb AU - Stephen G. Waxman AU - Sulayman D. Dib-Hajj Y1 - 2004/07/28 UR - http://www.jneurosci.org/content/24/30/6765.abstract N2 - Voltage-gated sodium channels interact with cytosolic proteins that regulate channel trafficking and/or modulate the biophysical properties of the channels. Nav1.6 is heavily expressed at the nodes of Ranvier along adult CNS and PNS axons and along unmyelinated fibers in the PNS. In an initial yeast two-hybrid screen using the C terminus of Nav1.6 as a bait, we identified FHF2B, a member of the FGF homologous factor (FHF) subfamily, as an interacting partner of Nav1.6. Members of the FHF subfamily share ∼70% sequence identity, and individual members demonstrate a cell- and tissue-specific expression pattern. FHF2 is abundantly expressed in the hippocampus and DRG neurons and colocalizes with Nav1.6 at mature nodes of Ranvier in myelinated sensory fibers in the dorsal root of the sciatic nerve. However, retinal ganglion cells and spinal ventral horn motor neurons show very low levels of FHF2 expression, and their axons exhibit no nodal FHF2 staining within the optic nerve and ventral root, respectively. Thus, FHF2 is selectively localized at nodes of dorsal root sensory but not ventral root motor axons. The coexpression of FHF2B and Nav1.6 in the DRG-derived cell line ND7/23 significantly increases the peak current amplitude and causes a 4 mV depolarizing shift of voltage-dependent inactivation of the channel. The preferential expression of FHF2B in sensory neurons may provide a basis for physiological differences in sodium currents that have been reported at the nodes of Ranvier in sensory versus motor axons. ER -