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Gene Review

NFASC  -  neurofascin

Homo sapiens

Synonyms: FLJ46866, KIAA0756, NF, NRCAML, Neurofascin
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Disease relevance of NFASC

  • On immunoblots of NF proteins, the antibodies recognized epitopes that were variably sensitive to Escherichia coli alkaline phosphatase [1].
  • On the contrary, overexpression of human NF-H proteins was found to confer an effective protection against mutant SOD1 toxicity in transgenic mice, a phenomenon that may be due to the ability of NF proteins to chelate calcium [2].
  • We examined cytoskeleton-associated forms of NF proteins during axonal neuritogenesis in cultured dorsal root ganglion (DRG) neurons and NB2a/d1 neuroblastoma [3].
  • These results indicate that the site of modification of the 190 kDa NF precursor to the 220 kDa axonal form is probably at the point where the axon initial segments leave the ganglion, which is several mm distal to its site of synthesis in the cell body [4].
  • However, the preponderance of phosphorylated NF epitopes as compared with nonphosphorylated forms in the cell bodies of carcinoid tumor cells implicates abnormal phosphorylation states in the formation of these intermediate filament aggregates [5].

High impact information on NFASC

  • One of these, CTF/NF I, is a multifunctional protein associated previously with activation of transcription and DNA replication [6].
  • To gain insights into how the expression of NF subunit proteins is regulated in vivo, two transgenes harboring coding sequences for human NFM (hNFM) with or without the hNFM multiphosphorylation repeat domain were introduced into mice [7].
  • Together with the recent identification of the serine in KSP as the main target for NF-directed protein kinases in vivo, this repetitive character explains the massive phosphorylation of the NF-H subunit that can occur in axons [8].
  • The human NF-H gene has three introns, two of which interrupt the protein-coding sequence at identical points to introns in the genes for the two smaller NF proteins, NF-M and NF-L.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
  • By using immunoprecipitation and MS, glucose-regulated protein 78/BiP and glucose-regulated protein 94 were identified as proteins that interact with NF-SLN through the RSYQY sequence [9].

Biological context of NFASC

  • Analysis of Fc fusion proteins representing different extracellular regions of NF indicate that NF186 inhibits cell adhesion and neurite outgrowth, and the inhibition is associated with the region containing the mucin-like domain [10].
  • We conclude that the secondary upregulation of NF message during axonal regeneration in the lamprey CNS may be part of an intrinsic growth program executed only in neurons with a strong propensity for regeneration [11].
  • Abnormal accumulations of neurofilaments (NFs) in motor neurons and a down-regulation of mRNA for the NF light subunit (NF-L) are associated with ALS, but it remains unclear to what extent these NF perturbations contribute to human disease [2].
  • These promoter fusion plasmids induced a significant level of beta-galactosidase in NF-nonproducing C6 cells as well as in NF-producing PC12h cells [12].
  • Four commercial kits, Oxi/Ferm (OF), API 20E (AP), Minitek (MT; BBL Microbiology Systems), and Flow N/F (NF), were evaluated, without additional tests, for identification of 258 gram-negative nonfermentative rods [13].

Anatomical context of NFASC

  • The Ig cell adhesion molecules (CAM) neurofascin (NF) and Nr-CAM are localized at developing nodes of Ranvier in peripheral myelinated axons prior to clustering of Na(+) channels [14].
  • The results suggest a critical early role for axonal NF in clustering of Na(+) channels at nodes of Ranvier via interactions with receptors on Schwann cells [14].
  • These changes indicate that an invasion of the dendrites by phosphorylated NFs may be linked to the destabilization of dendritic MTs, and in some dendrites this may lead to a marked loss of stable MTs, which is correlated with the emergence of NF-filled sprouts from the dendritic tips [15].
  • However, in the context of motor neuron disease caused by mutant SOD1, there is emerging evidence that NF proteins rather play a protective role [2].
  • The recovery of NF expression in good regenerators was independent of axon growth across the lesion, because excision of a segment of spinal cord caudal to the transection site blocked regeneration but did not prevent the return of NF-180 mRNA [11].

Associations of NFASC with chemical compounds

  • However, nuclear run-off assay revealed that the NF-L gene was not transcribed in NF-nonproducing C6 cells [12].
  • NF-SLN also decreased maximal Ca(2+) transport activity at pCa 5 by 31% with no significant change in apparent Ca(2+) affinity (6.36 +/- 0.07 versus 6.39 +/- 0.08 pCa units) [16].
  • Treatment with the protease inhibitor calpeptin increased overall NF subunits, but increased those within the GC to a greater extent than those along the shaft, indicating that subunits in the GC undergo more rapid turnover than do those within the shaft [17].
  • The cytoskeleton-enriched, Triton X-100 insoluble fraction was further separated into individual NF subunits using hydroxyapatite HPLC [18].
  • LR white post-embedding colloidal gold method to immunostain MBP, P0, NF and S100 in glutaraldehyde fixed peripheral nerve tissue [19].

Other interactions of NFASC

  • Neurofascin (NF) is a neural cell adhesion molecule in the L1-family containing six Ig domains and multiple fibronectin type III (FnIII) repeats in its extracellular region [10].
  • NF, conversely, is initially enriched in an ankyrin-independent manner in the axon generally and accumulates progressively in the initial segment attributable to preferential binding to ankG [20].

Analytical, diagnostic and therapeutic context of NFASC

  • To clarify the role of NF further, we analyzed effects of NF-Fc fusion proteins in Schwann cell-DRG neuron myelinating cocultures [14].
  • Immunofluorescence and immunoblotting of transfected cells by using anti-FLAG antibodies indicated that NF-SLN and PLN tagged at its N terminus with the FLAG epitope, even when overexpressed, were restricted to the ER [9].
  • The dendrites of anterior bulbar cells after close axotomy also show pronounced changes in NF protein and tubulin staining patterns prior to the emergence of sprouts from the dendrites [15].
  • During the first 4 weeks after operation, NF message levels were reduced dramatically in all axotomized reticulospinal neurons, on the basis of semiquantitative in situ hybridization for the single lamprey NF subunit (NF-180) [11].
  • Immunoreactive NF protein was seen largely in juxtanuclear globular aggregates which may correspond to cytoplasmic whorls of intermediate filaments observed in one of the tumors by electron microscopy [5].


  1. Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. Ksiezak-Reding, H., Dickson, D.W., Davies, P., Yen, S.H. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  2. Transgenic mice in the study of ALS: the role of neurofilaments. Julien, J.P., Couillard-Després, S., Meier, J. Brain Pathol. (1998) [Pubmed]
  3. Kinesin-mediated transport of neurofilament protein oligomers in growing axons. Yabe, J.T., Pimenta, A., Shea, T.B. J. Cell. Sci. (1999) [Pubmed]
  4. Characterization of the distinctive neurofilament subunits of the soma and axon initial segments in the squid stellate ganglion. Tytell, M., Pant, H.C., Gainer, H., Hill, W.D. J. Neurosci. Res. (1990) [Pubmed]
  5. Immunohistochemical demonstration of phosphorylated and nonphosphorylated forms of human neurofilament subunits in human pulmonary carcinoids. Christen, B., Trojanowski, J.Q., Pietra, G.G. Hum. Pathol. (1987) [Pubmed]
  6. Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters. Jones, K.A., Luciw, P.A., Duchange, N. Genes Dev. (1988) [Pubmed]
  7. Overexpression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. Tu, P.H., Elder, G., Lazzarini, R.A., Nelson, D., Trojanowski, J.Q., Lee, V.M. J. Cell Biol. (1995) [Pubmed]
  8. The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it. Lees, J.F., Shneidman, P.S., Skuntz, S.F., Carden, M.J., Lazzarini, R.A. EMBO J. (1988) [Pubmed]
  9. Sarcolipin retention in the endoplasmic reticulum depends on its C-terminal RSYQY sequence and its interaction with sarco(endo)plasmic Ca(2+)-ATPases. Gramolini, A.O., Kislinger, T., Asahi, M., Li, W., Emili, A., MacLennan, D.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186. Koticha, D., Babiarz, J., Kane-Goldsmith, N., Jacob, J., Raju, K., Grumet, M. Mol. Cell. Neurosci. (2005) [Pubmed]
  11. Recovery of neurofilament expression selectively in regenerating reticulospinal neurons. Jacobs, A.J., Swain, G.P., Snedeker, J.A., Pijak, D.S., Gladstone, L.J., Selzer, M.E. J. Neurosci. (1997) [Pubmed]
  12. Structure of the 68-kDa neurofilament gene and regulation of its expression. Nakahira, K., Ikenaka, K., Wada, K., Tamura, T., Furuichi, T., Mikoshiba, K. J. Biol. Chem. (1990) [Pubmed]
  13. Four methods for identification of gram-negative nonfermenting rods: organisms more commonly encountered in clinical specimens. Appelbaum, P.C., Stavitz, J., Bentz, M.S., von Kuster, L.C. J. Clin. Microbiol. (1980) [Pubmed]
  14. Neurofascin interactions play a critical role in clustering sodium channels, ankyrin(G) and betaIV spectrin at peripheral nodes of Ranvier. Koticha, D., Maurel, P., Zanazzi, G., Kane-Goldsmith, N., Basak, S., Babiarz, J., Salzer, J., Grumet, M. Dev. Biol. (2006) [Pubmed]
  15. Microtubule destabilization and neurofilament phosphorylation precede dendritic sprouting after close axotomy of lamprey central neurons. Hall, G.F., Lee, V.M., Kosik, K.S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  16. Sarcolipin overexpression in rat slow twitch muscle inhibits sarcoplasmic reticulum Ca2+ uptake and impairs contractile function. Tupling, A.R., Asahi, M., MacLennan, D.H. J. Biol. Chem. (2002) [Pubmed]
  17. Growth cones contain a dynamic population of neurofilament subunits. Chan, W.K., Yabe, J.T., Pimenta, A.F., Ortiz, D., Shea, T.B. Cell Motil. Cytoskeleton (2003) [Pubmed]
  18. Neurofilament metabolism in sporadic amyotrophic lateral sclerosis. Strong, M.J. J. Neurol. Sci. (1999) [Pubmed]
  19. LR white post-embedding colloidal gold method to immunostain MBP, P0, NF and S100 in glutaraldehyde fixed peripheral nerve tissue. Keita, M., Magy, L., Richard, L., Piaser, M., Vallat, J.M. J. Peripher. Nerv. Syst. (2002) [Pubmed]
  20. Ankyrin-dependent and -independent mechanisms orchestrate axonal compartmentalization of L1 family members neurofascin and L1/neuron-glia cell adhesion molecule. Boiko, T., Vakulenko, M., Ewers, H., Yap, C.C., Norden, C., Winckler, B. J. Neurosci. (2007) [Pubmed]
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