Neurofilament chains

In the medium and large neurofilament chains, where there are numerous K-S-P phosphorylation sites in the tail domains, the effect of phosphorylation is quite different. It has no visible effect on the state of filament assembly. It does, however, appear to be particularly important in determining axonal diameter (and concomitant conduction velocity), as well as transport properties and association with other cytoskeletal components. Experimentally, numerous phosphorylation sites have been shown to exist in a wide variety of IF proteins. Many others have been proposed on the basis of sequence motifs consistent with sites of known kinases. It has also been shown that mutations in which phosphorylation sites have been changed (see, for example, S35A in keratin 19) lead to various pathologies, including malformations in the filament assembly. 

Jordanova, A., De Jonghe, P., Boerkoel, C. F. et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain 126 590-597, 2003. 

The Ca2+-dependent neutral proteases called calpains are found within the cells of higher animals. The 705-residue multidomain peptide chain of a chicken calpain contains a papain-like domain as well as a calmodulin-like domain.328 It presumably arose from fusion of the genes of these proteins. At least six calpains with similar properties are known.329 Some have a preference for myofibrillar proteins or neurofilaments.330 They presumably function in normal turnover of these proteins and may play a role in numerous calcium-activated cellular processes.331-3323... 

There are multiple phosphorylation sites in the tail domain of the medium and high molecular weight chain of neurofilaments (NF-H). In the majority of cases, the phosphorylation sites are serine residues within the... 

Fig. 6. Schematic representation of the tail domains in Type IV intermediate filament chains. The rod domain, indicated by a shaded rectangle, does not show its known substructure. The four chains illustrated here are, from the top downwards, a-intemexin, and the low (NF-L), medium (NF-M), and high molecular weight chains (NF-FI) from neurofilaments. The characters of the segments are indicated by the one letter code. Figure is redrawn from Parry and Steinert (1995) and is based on an original by Shaw.

Frappier, T., Stetzkowski-Marden, F., and Pradel, L.-A. (1991). Interaction domains of neurofilament light chain and brain spectrin. Biochem. J. 275, 521-527. 

Table 7 lists S-100-positive tumors and their positivity with additional markers. Myelin basic protein (MBP) (30) is a single-chain polypeptide associated with the central and peripheral nervous system. Glial fibrillary acidic protein (GFAP) and neurofilament proteins (NFP) are intermediate filaments associated with glial cells and neural cells, respectively. HMB-45 is a mouse monoclonal antibody that reacts with an antigen present in premelanosomes. It is highly sensitive and specific for melanomas and certain nevi (junctional, congenital, blue nevi). EMA has been discussed in Section 3.1.3.1. 

Sachana, M, Flaskos, J., Alexaki, E.. and Hargreaves, A. J. (2001b). Inhibition of neurilc outgrowth in N2a cells by Icp-tophos and carbaryl Effects on neurofilament heavy chain. GAP-34 and HSP-70. Toxicol in VHto 15,115-120. 

Pellegrino GR, Berg JM (1991) Identification and characterization of zinc-finger domains by the polymerase chain reaction. Proc Natl Acad Sci USA 88 671-675 Reddy BA, Etkin LD, Freemont PS (1992) A neurofilament-specific sequence motif. TIBS 17 344-345... 

Immunostaining with SMI-31 antibody, which was originally made against the phosphorylated neurofilament heavy-chain protein, recognizes the phosphorylated tau (p-tau) of PHFs in s-IBM muscle and in Alzheimer brain on immunoblots [11, 12], and it... 

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