Tau splicing

Tauopathies are a group of disorders that are the consequence of abnormal tau phosphorylation, abnormal levels of tau, abnormal tau splicing, or mutations in the tau gene. These disorders are characterized not only by neuronal, but also oligo-dendroglial and astrocytic filamentous tau inclusions (Avila, 2000 Ulloa et al.,... 

Hutton, M., Lendon, C. L., Rizzu, P. et al. Association of missense and 5 -splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393 702-705,1998. 

Figure 9.25 Tracer studies on tau protein (a) ID gel, (b) 65Cu/63Cu isotope ratios in gel bands measured by LA-ICP-MS, (c) MALDI-FTICR mass spectrum of splice isoform tau F (). Su. Becker, M. Zoriy, M. Przybylski, ]. S. Becker, ]. Anal. At. Spectrom., 22, 63 (2007). Reproduced by permission of the Royal Society of Chemistry.)...

Mukai, F. Ishiguro, K. Sano, Y. Fujita, S.C. Alternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3. J. Neurochem., 81, 1073-1083 (2002)... 

Isolated microtubules always contain small amounts of larger 300-kDa microtubule-associated proteins (MAPS).330 These elongated molecules may in part lie in the grooves between the tubulin subunits and in part be extended outward to form a low-density layer around the tubule.283 309 Nerve cells that contain stable microtubules have associated stabilizing proteins.331 A family of proteins formed by differential splicing of mRNA are known as tau. The tau proteins are prominent components of the cytoskeleton of neurons. They not only interact with microtubules but also undergo reversible phosphorylation. Hyperphosphorylated tau is the primary component of the paired helical filaments found in the brains of persons with Alzheimer disease.330... 

HSP27 and Tau protein, respectively. 2D immunoblotting combined with mass spectrometry-based identification methods has been widely applied to the characterization of 2D electrophoretic cross-reactive isoforms of the same protein, e.g., resulting from alternative splicing, co- and/or posttranslational modifications and proteolytic cleavages (15-19). 

Varani, L., et al (1999). Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc. Natl. Acad. Sci. USA 96, 8229—8234. 

Tau forms up to six different isoforms by alternative splicing, and all six isoforms have been found in NFTs. Tau in NFT is typically hyperphosphorylated and in this state tubulin assembly is impaired. Hyperphosphorylated forms of tau have lower binding affinities to microtubules and may destabilise them. 

D Souza I, Poorkaj P, Hong M, NocUin D, Lee VM et si (1999) Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Nad Acad Sci USA 96 5598-5603... 

Kondo S, Yamcunoto N, Murakami T, Okumura M, Mayeda A et al (2004) Tra2 beta, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA. Genes Cells 9 121-130... 

Fig. 1 Schematic representation of the human tau gene (a), RNA (b), and brain tau isoforms (c). Alternatively spliced exons (2,3, and 10) are shown in orange, cream, and green, lespectiveiy. The tandem repeats (3 or 4) are shown in white bars. The number of aminoadds is indicated on the right-hand side (modified from SpUlantini and Goedert, 2000)...

Alonso AD, Zaidi T, Novak M, Barra HS, Grundke-Iqbal I, Iqbal K (2001) Interaction of tau isoforms with Alzheimer s disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-tike protein. J Biol Chem 276 37967-37973 Andreadis A (2006) Misregulation of tau alternative splicing in neurodegeneration and dementia. Prog Mol Subcell Biol 44 89-107... 

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