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Gene Review

Nfasc  -  neurofascin

Mus musculus

Synonyms: AA387016, D430023G06Rik, NF, Neurofascin, mKIAA0756
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High impact information on Nfasc

  • Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment [1].
  • Transgenic expression of Nfasc155 in the myelinating glia of Nfasc-/- nerves rescues the axoglial adhesion complex by recruiting the axonal proteins Caspr and Contactin to the paranodes [2].
  • It is composed of four structural elements: At the NH2 terminus neurofascin contains six Ig-like motifs of the C2 subcategory followed by four fibronectin type III (FNIII)-related repeats [3].
  • Between the FNIII-like repeats and the plasma membrane spanning region neurofascin contains a domain 75-amino acid residues-long rich in proline, alanine and threonine which might be the target of extensive O-linked glycosylation [3].
  • In contrast to NrCAM, the intracellular domains of the other mammalian L1 family molecules, e.g. L1, CHL1 and Neurofascin, did not interact with these PDZ domains [4].

Biological context of Nfasc

  • The formation of these specialized axoglial contacts depends on the presence of three cell adhesion molecules: neurofascin 155 on the glial membrane and a complex of Caspr and contactin on the axon [5].
  • Mice with ankyrin-G expression abolished in the cerebellum exhibit loss of ability of Purkinje neurons to fire action potentials, as well as loss of restriction of neurofascin/NrCAM to axon initial segments [6].

Anatomical context of Nfasc

  • In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin [7].
  • AnkyrinG 480/270 kDa and three ankyrin-binding integral membrane proteins (neurofascin, NrCAM, and the voltage-dependent sodium channel) colocalize within a specialized domain of the spectrin-actin network found at axonal segments of nodes of Ranvier in myelinated axons [8].

Other interactions of Nfasc

  • All four mRNAs are expressed in NSC-34 cells, but only neurofascin and the insert-minus form of L1 are expressed in its neuroblastoma parent, N18TG2 [9].

Analytical, diagnostic and therapeutic context of Nfasc

  • Northern blot analysis with domain specific probes showed that neurofascin mRNAs of about 8.5 kb are expressed throughout development in embryonic brain but not in liver [3].


  1. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Ango, F., di Cristo, G., Higashiyama, H., Bennett, V., Wu, P., Huang, Z.J. Cell (2004) [Pubmed]
  2. Neurofascins are required to establish axonal domains for saltatory conduction. Sherman, D.L., Tait, S., Melrose, S., Johnson, R., Zonta, B., Court, F.A., Macklin, W.B., Meek, S., Smith, A.J., Cottrell, D.F., Brophy, P.J. Neuron (2005) [Pubmed]
  3. Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily. Volkmer, H., Hassel, B., Wolff, J.M., Frank, R., Rathjen, F.G. J. Cell Biol. (1992) [Pubmed]
  4. The cytoplasmic domain of NrCAM binds to PDZ domains of synapse-associated proteins SAP90/PSD95 and SAP97. Dirks, P., Thomas, U., Montag, D. Eur. J. Neurosci. (2006) [Pubmed]
  5. Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton. Ogawa, Y., Schafer, D.P., Horresh, I., Bar, V., Hales, K., Yang, Y., Susuki, K., Peles, E., Stankewich, M.C., Rasband, M.N. J. Neurosci. (2006) [Pubmed]
  6. Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels. Bennett, V., Lambert, S. J. Neurocytol. (1999) [Pubmed]
  7. CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A. J. Neurosci. (2004) [Pubmed]
  8. Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates. Lambert, S., Davis, J.Q., Bennett, V. J. Neurosci. (1997) [Pubmed]
  9. Expression of four immunoglobulin superfamily adhesion molecules (L1, Nr-CAM/Bravo, neurofascin/ABGP, and N-CAM) in the developing mouse spinal cord. Moscoso, L.M., Sanes, J.R. J. Comp. Neurol. (1995) [Pubmed]
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