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Gene Review

NEFL  -  neurofilament, light polypeptide

Bos taurus

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Disease relevance of NEFL

  • We dephosphorylated NF-H using Escherichia coli alkaline phosphatase, then reassembled it into neurofilaments with NF-M and NF-L, and into NF-H filaments with NF-H alone [1].

High impact information on NEFL


Biological context of NEFL


Anatomical context of NEFL

  • The radioiodinated neurofilament proteins (untreated and dephosphorylated) were incubated in the presence and absence of calpain from rabbit skeletal muscle, and the degradation rates of large (NF-H), mid-sized (NF-M) and small (NF-L) neurofilament polypeptides were analysed by SDS/polyacrylamide-gel electrophoresis and autoradiography [9].
  • We carried out immunolabeling studies of purified bovine spinal cord neurofilaments (NFs) and filaments reconstituted from several combinations of the NF triplet polypeptides, NF-H, NF-M, and NF-L [10].
  • CKI from rabbit reticulocytes phosphorylated all three NF subunits (NF-H, NF-M and NF-L) [11].
  • Using the smallest subunit (NF-L) of a neurofilament and a glial fibrillary acidic protein, the subunit arrangement in intermediate filaments was studied by low-angle rotary shadowing [12].
  • In conclusion, NF-L in bovine chromaffin cells demonstrates that at least one neuronal trait persists in these catecholamine-producing cells of the mature adrenal gland [13].

Associations of NEFL with chemical compounds

  • Co-incubation of purified high (NF-H) and middle (NF-M) but not low (NF-L) molecular weight NF subunits prevents this AlCl3-induced alteration in electrophoretic migration [14].
  • In addition, much of this component was easily isolated on DE-52 column chromatography of the reassembled crude neurofilament proteins with buffers containing 6 M urea, while the low molecular weight component of the neurofilaments (NF-L, 70 kDa) was hardly detected [15].
  • Assembled NF-L filaments could also be phosphorylated by cyclic AMP dependent protein kinase indicating that the sites were accessible [7].

Enzymatic interactions of NEFL

  • In the native NF, A-kinase phosphorylated each NF subunit with stoichiometries of 4 mol/mol for NF-L, 6 mol/mol for NF-M, and 4 mol/mol for NF-H [3].

Other interactions of NEFL

  • Molecular mass information shows that there is one-half equivalent phosphate group on NFL and 24 on NFM [4].

Analytical, diagnostic and therapeutic context of NEFL

  • Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) shows molecular masses for bovine NFP subunits of 63, 105, and 125 kDa for NFL, NFM, and NFH [4].
  • Titration of NF-L with NF-M indicated that complex formation was complete at an approximately equimolar ratio of the two proteins [16].
  • Individual components of the NF triplet, i.e. NF-L, NF-M and NF-H, were purified by DE-52 and Mono-Q anion exchange chromatographies in the presence of 6 M-urea and were assembled in various combinations into filaments [17].
  • When rounded chromaffin cells in culture were examined, double-label immunofluorescence microscopy revealed an IFAP-300kDa/NF-L-positive juxtanuclear aggregate [18].


  1. Dephosphorylation of the largest neurofilament subunit protein influences the structure of crossbridges in reassembled neurofilaments. Gotow, T., Tanaka, T., Nakamura, Y., Takeda, M. J. Cell. Sci. (1994) [Pubmed]
  2. Assembly and exchange of intermediate filament proteins of neurons: neurofilaments are dynamic structures. Angelides, K.J., Smith, K.E., Takeda, M. J. Cell Biol. (1989) [Pubmed]
  3. Phosphorylation of native and reassembled neurofilaments composed of NF-L, NF-M, and NF-H by the catalytic subunit of cAMP-dependent protein kinase. Hisanaga, S., Matsuoka, Y., Nishizawa, K., Saito, T., Inagaki, M., Hirokawa, N. Mol. Biol. Cell (1994) [Pubmed]
  4. Identification of endogenous phosphorylation sites of bovine medium and low molecular weight neurofilament proteins by tandem mass spectrometry. Trimpin, S., Mixon, A.E., Stapels, M.D., Kim, M.Y., Spencer, P.S., Deinzer, M.L. Biochemistry (2004) [Pubmed]
  5. Brain micro glutamic acid-rich protein is the C-terminal endpiece of the neurofilament 68-kDa protein as determined by the primary sequence. Isobe, T., Okuyama, T. FEBS Lett. (1985) [Pubmed]
  6. Proline-directed protein kinase (p34cdc2/p58cyclin A) phosphorylates bovine neurofilaments. Guan, R.J., Hall, F.L., Cohlberg, J.A. J. Neurochem. (1992) [Pubmed]
  7. Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro. Nakamura, Y., Takeda, M., Angelides, K.J., Tanaka, T., Tada, K., Nishimura, T. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  8. Mortality of horn fly (Diptera: Muscidae) larvae in bovine dung supplemented with loline alkaloids from tall fescue. Dougherty, C.T., Knapp, F.W., Bush, L.P., Maul, J.E., Van Willigen, J. J. Med. Entomol. (1998) [Pubmed]
  9. Dephosphorylation of neurofilament proteins enhances their susceptibility to degradation by calpain. Pant, H.C. Biochem. J. (1988) [Pubmed]
  10. Antibody labeling of bovine neurofilaments: implications on the structure of neurofilament sidearms. Mulligan, L., Balin, B.J., Lee, V.M., Ip, W. J. Struct. Biol. (1991) [Pubmed]
  11. Bovine neurofilament-enriched preparations contain kinase activity similar to casein kinase I--neurofilament phosphorylation by casein kinase I (CKI). Link, W.T., Dosemeci, A., Floyd, C.C., Pant, H.C. Neurosci. Lett. (1993) [Pubmed]
  12. Molecular architecture of the neurofilament. I. Subunit arrangement of neurofilament L protein in the intermediate-sized filament. Hisanaga, S., Ikai, A., Hirokawa, N. J. Mol. Biol. (1990) [Pubmed]
  13. Immunomicroscopy of neurofilaments in chromaffin cells of the adult bovine adrenal gland. Yang, H.Y., Kriho, V., Lieska, N., Pappas, G.D. J. Comp. Neurol. (1996) [Pubmed]
  14. Multiple interactions of aluminum with neurofilament subunits: regulation by phosphate-dependent interactions between C-terminal extensions of the high and middle molecular weight subunits. Shea, T.B., Beermann, M.L. J. Neurosci. Res. (1994) [Pubmed]
  15. Isolation of a stable tetramer of the low molecular weight component of neurofilaments (NF-L). Tokutake, S., Tanaka, K. J. Biochem. (1989) [Pubmed]
  16. Neurofilament protein heterotetramers as assembly intermediates. Cohlberg, J.A., Hajarian, H., Tran, T., Alipourjeddi, P., Noveen, A. J. Biol. Chem. (1995) [Pubmed]
  17. Structure of the peripheral domains of neurofilaments revealed by low angle rotary shadowing. Hisanaga, S., Hirokawa, N. J. Mol. Biol. (1988) [Pubmed]
  18. Presence of a 300-kDa intermediate-filament-associated protein (IFAP-300kDa) in bovine chromaffin cells. Yang, H.Y., Kriho, V., Pappas, G.D. Exp. Neurol. (1996) [Pubmed]
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