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Gene Review

NEFM  -  neurofilament, medium polypeptide

Homo sapiens

Synonyms: 160 kDa neurofilament protein, NEF3, NF-M, NFM, Neurofilament 3, ...
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Disease relevance of NEFM

  • To test this hypothesis, we investigated LGI1 expression in parallel with expression of the neuronal marker NEF3 by real-time PCR on 30 malignant gliomas [1].
  • The pattern of expression of NF isoforms in PNETs was reminiscent of that seen during normal mammalian development, such that phosphorylated NF-H was only present in combination with NF-M and NF-L [2].
  • Findings in the present study suggest that atrophy, that is, the reduction in axonal calibre and paranodal demyelination, seen in leprous nerves may result from dephosphorylation of NF-H and NF-M proteins [3].
  • NEURO-2A neuroblastoma cells were differentiated by the addition of dibutyryl-cyclic AMP, resulting in an increase in transcription of mRNA coding for the two neurofilament polypeptides NF-L and NF-M [4].
  • None of the appendiceal carcinoid tumors expressed NF-M or NF-H, yet all of these tumors demonstrated immunoreactivity with CR [5].

Psychiatry related information on NEFM


High impact information on NEFM

  • Cells in which neurite formation was associated with Hel-N1 overexpression, also expressed increased levels of endogenous neurofilament M (NF-M) protein, which distributed along the neurites [7].
  • Analysis of the association of NF-M mRNA with the translational apparatus in Hel-N1 transfectants showed nearly complete recruitment to heavy polysomes, indicating that Hel-N1 caused an increase in translational initiation [7].
  • 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 [8].
  • Our results suggest that NF-M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis [9].
  • NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line [9].

Chemical compound and disease context of NEFM

  • Study of Al3+ binding and conformational properties of the alanine-substituted C-terminal domain of the NF-M protein and its relevance to Alzheimer's disease [10].

Biological context of NEFM

  • RFLP for BgI II at the human neurofilament medium chain (NEF3) gene locus [11].
  • The data suggest that hyperphosphorylation and tail domain O-glycosylation of NFs are synchronously regulated in axons of human neurons in situ and that O-glycosylation of NF-M is highly dynamic and closely interweaved with phosphorylation cascades and may have a pathophysiological role [12].
  • We generated a novel monoclonal antibody that specifically recognizes an O-glycosylated epitope in the tail domain of NF-M and allows determination of the glycosylation state at this residue [12].
  • 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)[13]
  • However, NF-H, NF-M, and NF-L were expressed throughout the cell cycle in dual parameter studies of D283 cells labeled with an antibody and propidium iodide [14].

Anatomical context of NEFM

  • The ratio of NF-M to NF-L was slightly decreased in cytoskeletons from the spinal cords of Klotho [15].
  • Thus, the coassembly between alpha-internexin and NF-M exhibits some unique characteristics previously not observed with other intermediate filament proteins: only one intact tail and one intact head are required for the formation of a normal filament network, and they can be present within the same partner or separately in two partners [16].
  • One hour after death, enhanced perikaryal immunostaining of NF-M and both phosphorylated and nonphosphorylated NF-H epitopes was observed throughout the hippocampal formation [17].
  • When cytoskeleton preparations were exposed to aluminum salt concentrations of 100 microM or higher, proportions of NF-M and NF-H formed urea-insoluble complexes of high apparent molecular mass, which were also resistant to proteolysis by calpain [18].
  • The middle molecular weight NF subunit (NF-M) and tau were extensively represented in SP neurites, i.e., epitopes extending from the NH2 to COOH domains of NF-M and tau were present [19].

Associations of NEFM with chemical compounds

  • Upon differentiation of SHSY5Y cells with retinoic acid, we found that the phosphorylation of high molecular mass (NF-H) and medium molecular mass (NF-M) NFs increased, whereas the CDK-5 protein level and kinase activity were unaffected [20].
  • Following a 15 min pulse radiolabeling, NF-H isoforms migrating from approximately 160-200 kDa, NF-M isoforms migrating from approximately 97 k-145 Da, and a single 70 kDa NF-L isoform were readily detectable within Triton-soluble fractions from both undifferentiated and differentiated cells [21].
  • Cerebral cortex exhibited elevated levels of both NF-L and NF-M transcripts in DFP-treated hens throughout the period of observation [22].
  • We report here that both NF-M-dependent promoter constructs and resident genes could be activated by addition of beta-estradiol to the NF-M-estrogen receptor expressing progenitors [9].
  • NB2a/d1 cells differentiated with dibutyryl cAMP were transfected with constructs expressing Vm or the middle-molecular-weight NF subunit (NF-M) each conjugated to green fluorescent protein (GFP) [23].

Regulatory relationships of NEFM

  • The low (NF-L) and middle (NF-M) molecular weight (Mr) neurofilament (NF) subunits are expressed before the high (NF-H) Mr NF subunit in embryonic neurons [14].

Other interactions of NEFM

  • Except for these Lys-Ser-Pro motifs, there is surprisingly little structural similarity between the squid NF-220 protein and mammalian NF-M and NF-H proteins [24].
  • Expression of marker proteins including beta-III-tubulin, alpha-internexin, NF-L and NF-M, tau and L1 indicated the neurons were differentiated, and in some cases polarized [25].
  • When cultured under conditions that promote neural differentiation, the cells adopted neuronal morphologies and expressed neuronal genes, including Gap-43, NF-M, tau, and synaptophysin [26].
  • Mammalian neurons and neuron-like cultured cells express the neural intermediate filament (IF) proteins neurofilament (NF)-L, NF-M, NF-H, and peripherin [27].
  • Levels of all three NF subunits and the degree of phosphorylation of NF-H and NF-M were significantly increased in AD as compared to Huntington disease brains used as control tissue [28].

Analytical, diagnostic and therapeutic context of NEFM


  1. Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI1. Piepoli, T., Jakupoglu, C., Gu, W., Lualdi, E., Suarez-Merino, B., Poliani, P.L., Cattaneo, M.G., Ortino, B., Goplen, D., Wang, J., Mola, R., Inverardi, F., Frassoni, C., Bjerkvig, R., Steinlein, O., Vicentini, L.M., Brüstle, O., Finocchiaro, G. Neuro-oncology (2006) [Pubmed]
  2. Molecular markers of primitive neuroectodermal tumors and other pediatric central nervous system tumors. Monoclonal antibodies to neuronal and glial antigens distinguish subsets of primitive neuroectodermal tumors. Molenaar, W.M., Jansson, D.S., Gould, V.E., Rorke, L.B., Franke, W.W., Lee, V.M., Packer, R.J., Trojanowski, J.Q. Lab. Invest. (1989) [Pubmed]
  3. Alterations in neurofilament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study. Save, M.P., Shetty, V.P., Shetty, K.T., Antia, N.H. Neuropathol. Appl. Neurobiol. (2004) [Pubmed]
  4. Temporal expression of neurofilament polypeptides in differentiating neuroblastoma cells. Breen, K.C., Anderton, B.H. Neuroreport (1991) [Pubmed]
  5. Neurofilament and chromogranin expression in normal and neoplastic neuroendocrine cells of the human gastrointestinal tract and pancreas. Perez, M.A., Saul, S.H., Trojanowski, J.Q. Cancer (1990) [Pubmed]
  6. Cytoskeletal neurofilament gene expression in brain tissue from Alzheimer's disease patients. I. Decrease in NF-L and NF-M message. Kittur, S., Hoh, J., Endo, H., Tourtellotte, W., Weeks, B.S., Markesbery, W., Adler, W. Journal of geriatric psychiatry and neurology. (1994) [Pubmed]
  7. ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells. Antic, D., Lu, N., Keene, J.D. Genes Dev. (1999) [Pubmed]
  8. 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]
  9. NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line. Müller, C., Kowenz-Leutz, E., Grieser-Ade, S., Graf, T., Leutz, A. EMBO J. (1995) [Pubmed]
  10. Study of Al3+ binding and conformational properties of the alanine-substituted C-terminal domain of the NF-M protein and its relevance to Alzheimer's disease. Shen, Z.M., Perczel, A., Hollósi, M., Nagypál, I., Fasman, G.D. Biochemistry (1994) [Pubmed]
  11. RFLP for BgI II at the human neurofilament medium chain (NEF3) gene locus. Ding, Y., Reed, D.R., Baltazar, M.C., Price, R.A. Nucleic Acids Res. (1992) [Pubmed]
  12. O-glycosylation of the tail domain of neurofilament protein M in human neurons and in spinal cord tissue of a rat model of amyotrophic lateral sclerosis (ALS). Lüdemann, N., Clement, A., Hans, V.H., Leschik, J., Behl, C., Brandt, R. J. Biol. Chem. (2005) [Pubmed]
  13. 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]
  14. Phosphate-dependent and independent neurofilament protein epitopes are expressed throughout the cell cycle in human medulloblastoma (D283 MED) cells. Trojanowski, J.Q., Kelsten, M.L., Lee, V.M. Am. J. Pathol. (1989) [Pubmed]
  15. Neurofilaments of Klotho, the mutant mouse prematurely displaying symptoms resembling human aging. Uchida, A., Komiya, Y., Tashiro, T., Yorifuji, H., Kishimoto, T., Nabeshima, Y., Hisanaga, S. J. Neurosci. Res. (2001) [Pubmed]
  16. Roles of head and tail domains in alpha-internexin's self-assembly and coassembly with the neurofilament triplet proteins. Ching, G.Y., Liem, R.K. J. Cell. Sci. (1998) [Pubmed]
  17. Perikaryal accumulation and proteolysis of neurofilament proteins in the post-mortem rat brain. Geddes, J.W., Bondada, V., Tekirian, T.L., Pang, Z., Siman, R.G. Neurobiol. Aging (1995) [Pubmed]
  18. Aluminum inhibits calpain-mediated proteolysis and induces human neurofilament proteins to form protease-resistant high molecular weight complexes. Nixon, R.A., Clarke, J.F., Logvinenko, K.B., Tan, M.K., Hoult, M., Grynspan, F. J. Neurochem. (1990) [Pubmed]
  19. Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads. Schmidt, M.L., Lee, V.M., Trojanowski, J.Q. Lab. Invest. (1991) [Pubmed]
  20. CDK-5-mediated neurofilament phosphorylation in SHSY5Y human neuroblastoma cells. Sharma, M., Sharma, P., Pant, H.C. J. Neurochem. (1999) [Pubmed]
  21. Differential synthesis and cytoskeletal deposition of neurofilament subunits before and during axonal outgrowth in NB2a/d1 cells: evidence that segregation of phosphorylated subunits within the axonal cytoskeleton involves selective deposition. Shea, T.B. J. Neurosci. Res. (1995) [Pubmed]
  22. Enhanced mRNA expression of neurofilament subunits in the brain and spinal cord of diisopropyl phosphorofluoridate-treated hens. Gupta, R.P., Lin, W.W., Abou-Donia, M.B. Biochem. Pharmacol. (1999) [Pubmed]
  23. Reexpression of vimentin in differentiated neuroblastoma cells enhances elongation of axonal neurites. Dubey, M., Hoda, S., Chan, W.K., Pimenta, A., Ortiz, D.D., Shea, T.B. J. Neurosci. Res. (2004) [Pubmed]
  24. A high-molecular-weight squid neurofilament protein contains a lamin-like rod domain and a tail domain with Lys-Ser-Pro repeats. Way, J., Hellmich, M.R., Jaffe, H., Szaro, B., Pant, H.C., Gainer, H., Battey, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  25. Identification and characterization of a population of motile neurons in long-term cortical culture. Haas, M.A., Chuckowree, J.A., Chung, R.S., Vickers, J.C., Dickson, T.C. Cell Motil. Cytoskeleton (2007) [Pubmed]
  26. Long-term cryopreserved amniocytes retain proliferative capacity and differentiate to ectodermal and mesodermal derivatives in vitro. Woodbury, D., Kramer, B.C., Reynolds, K., Marcus, A.J., Coyne, T.M., Black, I.B. Mol. Reprod. Dev. (2006) [Pubmed]
  27. Some neural intermediate filaments contain both peripherin and the neurofilament proteins. Parysek, L.M., McReynolds, M.A., Goldman, R.D., Ley, C.A. J. Neurosci. Res. (1991) [Pubmed]
  28. Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells. Wang, J., Tung, Y.C., Wang, Y., Li, X.T., Iqbal, K., Grundke-Iqbal, I. FEBS Lett. (2001) [Pubmed]
  29. Epitopes located in spatially separate domains of each neurofilament subunit are present in Parkinson's disease Lewy bodies. Hill, W.D., Lee, V.M., Hurtig, H.I., Murray, J.M., Trojanowski, J.Q. J. Comp. Neurol. (1991) [Pubmed]
  30. Identification of a neurofilament-like protein in the protocerebral tract of the crab Ucides cordatus. Corrêa, C.L., da Silva, S.F., Lowe, J., Tortelote, G.G., Einicker-Lamas, M., Martinez, A.M., Allodi, S. Cell Tissue Res. (2004) [Pubmed]
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