| First Author | Xiao M | Year | 2013 |
| Journal | Mol Cell Neurosci | Volume | 56 |
| Pages | 393-403 | PubMed ID | 23891806 |
| Mgi Jnum | J:214016 | Mgi Id | MGI:5587871 |
| Doi | 10.1016/j.mcn.2013.07.008 | Citation | Xiao M, et al. (2013) FGF14 localization and organization of the axon initial segment. Mol Cell Neurosci 56:393-403 |
| abstractText | The axon initial segment (AIS) is highly enriched in the structural proteins ankyrin G and betaIV-spectrin, the pore-forming (alpha) subunits of voltage-gated sodium (Nav) channels, and functional Nav channels, and is critical for the initiation of action potentials. We previously reported that FGF14, a member of the intracellular FGF (iFGF) sub-family, is expressed in cerebellar Purkinje neurons and that the targeted inactivation of Fgf14 in mice (Fgf14(-/-)) results in markedly reduced Purkinje neuron excitability. Here, we demonstrate that FGF14 immunoreactivity is high in the AIS of Purkinje neurons and is distributed in a decreasing, proximal to distal, gradient. This pattern is evident early in the postnatal development of Purkinje neurons and is also observed in many other types of central neurons. In (Scn8a(med)) mice, which are deficient in expression of the Nav1.6 alpha subunit, FGF14 immunoreactivity is markedly increased and expanded in the Purkinje neuron AIS, in parallel with increased expression of the Nav1.1 (Scn1a) alpha subunit and expanded expression of betaIV-spectrin. Although Nav1.1, FGF14, and betaIV-spectrin are affected, ankyrin G immunoreactivity at the AIS of Scn8a(med) and wild type (WT) Purkinje neurons was not significantly different. In Fgf14(-/-) Purkinje neurons, betaIV-spectrin and ankyrin G immunoreactivity at the AIS were also similar to WT Purkinje neurons, although both the Nav1.1 and Nav1.6 alpha subunits are modestly, but significantly (p<0.005), reduced within sub-domains of the AIS, changes that may contribute to the reduced excitability of Fgf14(-/-) Purkinje neurons. |
