Function and Evolution of Neurofilament Proteins<sup>a</sup>

Lasek, Raymond J.; Phillips, Linda R.; Katz, Michael J.; Autilio-Gambetti, L.

doi:10.1111/j.1749-6632.1985.tb50429.x

Cited by 96 publications

(54 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are several factors that could contribute to differential changes in members of the marker panel, including differences in their brain regional, cellular, and subcellular localizations, as well as possible different rates of turnover in the lumbar CSF. For example, phosphorylated NFH is localized primarily in axons (Jung et al, 2000), where it is part of the cytoskeleton (Sternberger et al, 1982;Lasek et al, 1985), whereas 14-3-3 βand ζ are cytoplasmic proteins concentrated in perikarya (Martin et al, 1994;Aitken et al, 2003). The five proteins are also differentially expressed across the neuraxis.…”

Section: Discussionmentioning

confidence: 98%

“…The validity of this approach was established by immunodetection of released proteins in CSF following experimental traumatic brain injury or transient global forebrain ischemia 2005). Several of these are expressed predominantly or exclusively in neurons, including the β and ζ isoforms of 14-3-3 (Aitken et al, 2003), a hypophosphorylated form of the neurofilament triplet polypeptide NFH (pNFH; Lasek et al, 1985;Jung et al, 2000), and the deubiquitinating enzyme UCH-L1 (Doran et al, 1983). Others are proteolytic fragments of abundant neuronal proteins, including an α-spectrin breakdown product generated by calpain, a family of calcium-dependent proteases associated with neuronal necrosis (Siman et al, 1989;Roberts-Lewis et al, 1993;Zhang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

et al. 2008

View full text Add to dashboard Cite

Previously, we identified 14-3-3 β and ζ isoforms and proteolytic fragments of α-spectrin as proteins released from degenerating neurons that also rise markedly in cerebrospinal fluid (CSF) following experimental brain injury or ischemia in rodents, but these proteins have not been studied before as potential biomarkers for ischemic central nervous system injury in humans. Here we describe longitudinal analysis of these proteins along with the neuron-enriched hypophosphorylated neurofilament H (pNFH) and the deubiquitinating enzyme UCH-L1 in lumbar CSF samples from 19 surgical cases of aortic aneurysm repair, 7 involving cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA). CSF levels of the proteins were near the lower limit of detection by Western blot or enzyme-linked fluorescence immunoassay at the onset of surgical procedures, but increased substantially in a subset of cases, typically within 12-24 hours. All cases involving DHCA were characterized by >3-fold elevations in CSF levels of the two 14-3-3 isoforms, UCH-L1, and pNFH. Six of 7 also exhibited marked increases in α-spectrin fragments generated by calpain, a protease known to trigger necrotic neurodegeneration. Among cases involving aortic cross-clamping but not DHCA, the proteins rose in CSF preferentially in the subset experiencing acute neurological complications. Our results suggest the neuron-enriched 14-3-3β, 14-3-3ζ, pNFH, UCH-L1, and calpain-cleaved α-spectrin may serve as a panel of biomarkers with clinical potential for the detection and management of ischemic central nervous system injury, including for mild damage associated with surgically-induced circulation arrest.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This reinforces the conclusion, based on the identification of cell lines without cIFs and the results of experimental studies (see below) that cIFs are not an indispensible feature of eukaryotic cells. On the other hand, cIFs have been found in essentially all the major multicellular eukaryotic phyla (Table I) [see Lasek et al, 1985;Traub, 1985;Biessman and Walter, 19891, and similarly sized cytoplasmic filaments, distinct from microfilaments and microtubules, have been identified in a number of protists [see Grain, 1986, for review]. For example, cytoplasmic filaments presumed to be related to vertebrate cIFs have been found associated with the oral apparatus of the ciliated protist Tetruhymenu [Numata et al, 19831. Proteins that cross react immunologically with the cIF subunit proteins of vertebrates have been found associated with microtubules in higher plant cells [Dawson et al, 1985;Hargreaves et al, 1989a,b].…”

Section: Phylogenetic Distribution Of If Proteinsmentioning

confidence: 99%

Functions of intermediate filaments

Klymkowsky

Bachant

Domingo

1989

Cell Motil. Cytoskeleton

179

View full text Add to dashboard Cite

“…However, because mRNA transcripts in general lack promoter sequences, the integration of an intronless cDNA molecule into the host chromosome usually results in the generation of a nontranscribed processed pseudogene that, with the passage of time, acquires mutations and thereby loses homology with its parental transcribed sequence (19 (Fig. 4), the time at which this event might have occurred is sufficiently distant (at least 600 million years ago, based on its presence in vertebrates, annelids, and molluscs [18]) so that all traces of the molecular event [flanking direct repeats and a poly(A) tract] would have been obliterated by neutral drift. In addition, the original intronless sequence would have had to acquire three new introns, presumably by insertional transposition, subsequent to its own creation.…”

mentioning

confidence: 99%

Anomalous placement of introns in a member of the intermediate filament multigene family: an evolutionary conundrum.

Lewis¹,

Cowan²

1986

Mol. Cell. Biol.

167

View full text Add to dashboard Cite

The origin of introns and their role (if any) in gene expression, in the evolution of the genome, and in the generation of new expressed sequences are issues that are understood poorly, if at all. Multigene families provide a favorable opportunity for examining the evolutionary history of introns because it is possible to identify changes in intron placement and content since the divergence of family members from a common ancestral sequence. Here we report the complete sequence of the gene encoding the 68-kilodalton (kDa) neurofilament protein, the gene is a member of the intermediate filament multigene family that diverged over 600 million years ago. Five other members of this family (desmin, vimentin, glial fibrillary acidic protein, and type I and type H keratins) are encoded by genes with six or more introns at homologous positions. To our surprise, the number and placement of introns in the 68-kDa neurofilament protein gene were completely anomalous, with only three introns, none of which corresponded in position to introns in any characterized intermediate filament gene. This finding was all the more unexpected because comparative amino acid sequence data suggest a closer relationship of the 68-kDa neurofilament protein to desmin, vimentin, and glial fibrillary acidic protein than between any of these three proteins and the keratins. It appears likely that an mRNA-mediated transposition event was involved in the evolution of the 68-kDa neurofilament protein gene and that subsequent events led to the acquisition of at least two of the three introns present in the contemporary sequence.Multigene families encoding groups of structurally or functionally related polypeptides are widespread in the genomes of eucaryotes. This is true both for proteins that are expressed in most if not all cell types (e.g., histones, actins, and tubulins) and proteins that show restricted patterns of tissue-specific expression (e.g., globins and immunoglobulins). In all cases, structural homologies evident at either the protein or DNA level (or both) point to the divergence of members of a given multigene family from a single primordial sequence. The extent of divergence depends upon selective constraints. Where function has remained similar (if not identical) over evolutionary time, the extent of divergence has been small (e.g., actins and tubulins [3,6]), with only relatively minor differences distinguishing one expressed member of the multigene family from another. Where functional demand has required diversity (e.g., immunoglobulin C regions), the extent of divergence has been greater (29).

show abstract

Function and Evolution of Neurofilament Proteins^a

Cited by 96 publications

References 45 publications

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

Functions of intermediate filaments

Anomalous placement of introns in a member of the intermediate filament multigene family: an evolutionary conundrum.

Contact Info

Product

Resources

About

Function and Evolution of Neurofilament Proteinsa

Cited by 96 publications

References 45 publications

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

Functions of intermediate filaments

Anomalous placement of introns in a member of the intermediate filament multigene family: an evolutionary conundrum.

Contact Info

Product

Resources

About

Function and Evolution of Neurofilament Proteins^a