NFASC explained

Neurofascin is a protein that in humans is encoded by the NFASC gene.^{[1] [2] [3]}

Function

Neurofascin is an L1 family immunoglobulin cell adhesion molecule (see L1CAM) involved in axon subcellular targeting and synapse formation during neural development.^{[3] [4]}

Clinical importance

A homozygous mutation causing loss of Nfasc155 causes severe congenital hypotonia, contractures of fingers and toes and no reaction to touch or pain.^[5]

Further reading

• Hortsch M . The L1 family of neural cell adhesion molecules: old proteins performing new tricks . Neuron . 17 . 4 . 587–93 . October 1996 . 8893017 . 10.1016/S0896-6273(00)80192-0 . 9625203 . free .
• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Research . 9 . 3 . 99–106 . June 2002 . 12168954 . 10.1093/dnares/9.3.99 . 10.1.1.500.923 .
• Tuvia S, Garver TD, Bennett V . The phosphorylation state of the FIGQY tyrosine of neurofascin determines ankyrin-binding activity and patterns of cell segregation . Proceedings of the National Academy of Sciences of the United States of America . 94 . 24 . 12957–62 . November 1997 . 9371782 . 24245 . 10.1073/pnas.94.24.12957 . 1997PNAS...9412957T . free .
• Ren Q, Bennett V . Palmitoylation of neurofascin at a site in the membrane-spanning domain highly conserved among the L1 family of cell adhesion molecules . Journal of Neurochemistry . 70 . 5 . 1839–49 . May 1998 . 9572267 . 10.1046/j.1471-4159.1998.70051839.x . free .
• Zhang X, Davis JQ, Carpenter S, Bennett V . Structural requirements for association of neurofascin with ankyrin . The Journal of Biological Chemistry . 273 . 46 . 30785–94 . November 1998 . 9804856 . 10.1074/jbc.273.46.30785 . free .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 5 . 5 . 277–86 . October 1998 . 9872452 . 10.1093/dnares/5.5.277 . free .
• Koroll M, Rathjen FG, Volkmer H . The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity . The Journal of Biological Chemistry . 276 . 14 . 10646–54 . April 2001 . 11152476 . 10.1074/jbc.M010647200 . free.
• Ratcliffe CF, Westenbroek RE, Curtis R, Catterall WA . Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain . The Journal of Cell Biology . 154 . 2 . 427–34 . July 2001 . 11470829 . 2150779 . 10.1083/jcb.200102086 .
• Jenkins SM, Kizhatil K, Kramarcy NR, Sen A, Sealock R, Bennett V . FIGQY phosphorylation defines discrete populations of L1 cell adhesion molecules at sites of cell-cell contact and in migrating neurons . Journal of Cell Science . 114 . Pt 21 . 3823–35 . November 2001 . 10.1242/jcs.114.21.3823 . 11719549 .
• Jenkins SM, Bennett V . Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments . The Journal of Cell Biology . 155 . 5 . 739–46 . November 2001 . 11724816 . 2150881 . 10.1083/jcb.200109026 .
• Charles P, Tait S, Faivre-Sarrailh C, Barbin G, Gunn-Moore F, Denisenko-Nehrbass N, Guennoc AM, Girault JA, Brophy PJ, Lubetzki C . Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction . Current Biology . 12 . 3 . 217–20 . February 2002 . 11839274 . 10.1016/S0960-9822(01)00680-7 . 18017227 . free . 2002CBio...12..217C .
• Kizhatil K, Wu YX, Sen A, Bennett V . A new activity of doublecortin in recognition of the phospho-FIGQY tyrosine in the cytoplasmic domain of neurofascin . The Journal of Neuroscience . 22 . 18 . 7948–58 . September 2002 . 12223548 . 10.1523/jneurosci.22-18-07948.2002. 6758080 .
• Gollan L, Salomon D, Salzer JL, Peles E . Caspr regulates the processing of contactin and inhibits its binding to neurofascin . The Journal of Cell Biology . 163 . 6 . 1213–8 . December 2003 . 14676309 . 2173730 . 10.1083/jcb.200309147 .

Notes and References

1. Volkmer H, Hassel B, Wolff JM, Frank R, Rathjen FG . Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily . The Journal of Cell Biology . 118 . 1 . 149–61 . July 1992 . 1377696 . 2289533 . 10.1083/jcb.118.1.149 .
2. Burmeister M, Ren Q, Makris GJ, Samson D, Bennett V . Genes for the neuronal immunoglobulin domain cell adhesion molecules neurofascin and Nr-CAM map to mouse chromosomes 1 and 12 and homologous human chromosomes . Mammalian Genome . 7 . 7 . 558–9 . July 1996 . 8672144 . 10.1007/s003359900168 . 29190292 .
3. Web site: Entrez Gene: NFASC neurofascin homolog (chicken).
4. Ango F, di Cristo G, Higashiyama H, Bennett V, Wu P, Huang ZJ . Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment . Cell . 119 . 2 . 257–72 . October 2004 . 15479642 . 10.1016/j.cell.2004.10.004 . 16245348 . free .
5. Smigiel R, Sherman DL, Rydzanicz M, Walczak A, Mikolajkow D, Krolak-Olejnik B, Kosinska J, Gasperowicz P, Biernacka A, Stawinski P, Marciniak M, Andrzejewski W, Boczar M, Krajewski P, Sasiadek MM, Brophy PJ, Ploski R . Homozygous mutation in the Neurofascin gene affecting the glial isoform of Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia . Human Molecular Genetics . 27. 21. August 2018 . 30124836 . 10.1093/hmg/ddy277 . 6196652 . 3669–3674.