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

• Cytoskeletal neurofilament gene expression in brain tissue from Alzheimer's disease patients. I. Decrease in NF-L and NF-M message [6].

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

• By flow cytometry, more than 90% of the D283 cells expressed NF-H and NF-M in different states of phosphorylation, and an antiserum specific for the carboxy terminus of NF-L labeled more than 60% of these cells [14].
• This study sought to determine the extent to which each neurofilament subunit [low (NF-L), mid (NF-M), or high (NF-H)] was present in Lewy bodies by using light, confocal, and electron microscopy [29].
• In order to confirm the results obtained with the immunohistochemical reactions, Western blotting, using the three primary antibodies, was performed and the presence of NF-M was confirmed [30].
• Conventional transmission electron microscopy was used to observe the ultrastructural components of the axons and immunoelectron microscopy was used to show the distribution of the NF-M-like polypeptides along cytoskeletal elements of the PCT [30].
• Using a specific antibody (SMI 31), the state of phosphorylation of high and medium molecular weight neurofilaments (NF-H and NF-M) was studied in 22 leprous and four nonleprous human peripheral nerves by means of immunohistochemistry, sodium dodecyl sulfate-poly acrylamide gel electrophoresis (SDS-PAGE) and Western immunoblot (WB) [3].

References