Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain.

Abstract

We have isolated cDNA clones encoding a 383‐amino acid isoform of the human microtubule‐associated protein tau. It differs from previously determined tau sequences by the presence of an additional repeat of 31 amino acids, giving four, rather than three, tandem repeats in its carboxy‐terminal half. The extra repeat is encoded by a separate exon. Probes derived from cDNA clones encoding the three (type I) and four repeat (type II) tau protein isoforms detected mRNAs for both forms in all adult human brain areas examined. However, in foetal brain only type I mRNA was found. Type I and type II mRNAs were present in pyramidal cells in cerebral cortex. In the hippocampal formation, type I mRNA was found in pyramidal and granule cells; type II mRNA was detected in most, though not all, pyramidal cells but not in granule cells. These observations indicate that tau protein mRNAs are expressed in a stage‐ and cell‐specific manner. Tau protein is found in the protease‐resistant core of the paired helical filament, the major constituent of the neurofibrillary tangle in Alzheimer's disease. Taken in conjunction with previous findings, the present results indicate that both the three and four repeat‐containing tau protein isoforms are present in the core of the paired helical filament.

Tau could protect DNA double helix structure

“…Fortunately, the absorbance (240 -300 nm) of tau at the concentrations used in this study was less than 0.05 at room temperature (data not shown). Such a low absorbance was mainly because the primary structure of tau did not contain any Trp residues [22], and thus, the absorbance of tau is in background.…”

SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations

“…Exon 10 modulates the C-terminus of the tau protein and encodes an additional microtubule binding domain (Lee et al, 1989). Exon 10 is adultspecific in rodents and humans (Goedert et al, 1989a(Goedert et al, , 1989bKosik et al, 1989) but with a crucial difference relevant to neurodegeneration: in adult rodents, exon 10 becomes constitutive . In contrast, in adult humans exon 10 remains regulated in the central nervous system where the two possible isoforms (10 + and 10 − ) are present in a 1:1 ratio (Gao et al, 2000;Goedert et al, 1989b).…”

“…Exon 10 is adultspecific in rodents and humans (Goedert et al, 1989a(Goedert et al, , 1989bKosik et al, 1989) but with a crucial difference relevant to neurodegeneration: in adult rodents, exon 10 becomes constitutive . In contrast, in adult humans exon 10 remains regulated in the central nervous system where the two possible isoforms (10 + and 10 − ) are present in a 1:1 ratio (Gao et al, 2000;Goedert et al, 1989b). The domain encoded by exon 10 increases the affinity of tau protein to microtubules and may be important in the transition from the more fluid fetal cytoskeleton to the more stable adult one (Himmler et al, 1989;Lee et al, 1989;Mandelkow et al, 1995).…”

Modulation of Microtubule Dynamics by Tau in Living Cells: Implications for Development and Neurodegeneration

“…First, although only 3-repeat tau is expressed in fetal brain, both 3-and 4-repeat tau are expressed in adult human brain at approximately equal levels (Goedert et al, 1989a(Goedert et al, , 1989bHimmler, 1989;Himmler et al, 1989;Kosik et al, 1989). It has been hypothesized that these expression differences generate different microtubule behavior in fetal neurons undergoing axonal outgrowth, pathfinding, and synpatogenesis vs. relatively stable adult neurons.…”