The alternative splicing of tau exon 10 and its regulatory proteins CLK2 and TRA2-BETA1 changes in sporadic Alzheimer's disease
Authors
Glatz, Daniela C.Rujescu, Dan
Tang, Yesheng
Berendt, Frank J.
Hartmann, Annette M.
Faltraco, Frank
Rosenberg, Carlyn
Hulette, Christine
Jellinger, Kurt
Hampel, Harald
Riederer, Peter
Moller, Hans-J
Andreadis, Athena
Henkel, Kerstin
Stamm, Stefan
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2005-12-24Keywords
AgedAged, 80 and over
*Alternative Splicing
Alzheimer Disease
Antigens, CD46
Blotting, Northern
Brain
Case-Control Studies
Exons
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Models, Biological
Postmortem Changes
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinases
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Transfection
tau Proteins
Cell Biology
Metadata
Show full item recordAbstract
Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in tauopathies, which include Alzheimer's disease (AD). Tau is a microtubule-associated protein whose transcript undergoes alternative splicing in the brain. Exon 10 encodes one of four microtubule-binding repeats. Exon 10 inclusion gives rise to tau protein isoforms containing four microtubule-binding repeats (4R) whereas exclusion leads to isoforms containing only three repeats (3R). The ratio between 3R and 4R isoforms is tightly controlled via alternative splicing in the human adult nervous system and distortion of this balance results in neurodegeneration. Previous studies showed that several splicing regulators, among them hTRA2-beta1 and CLK2, regulate exon 10 alternative splicing. Like most splicing factors, htra2-beta and clk2 pre-mRNAs are regulated by alternative splicing. Here, we investigated whether human postmortem brain tissue of AD patients reveal differences in alternative splicing patterns of the tau, htra2-beta, presenilin 2 and clk2 genes when compared with age-matched controls. We found that the splicing patterns of all four genes are altered in affected brain areas of sporadic AD patients. In these affected areas, the amount of mRNAs of tau isoforms including exon 10, the htra2-beta1 isoform and an inactive form of clk2 are significantly increased. These findings suggest that a misregulation of alternative splicing seems to contribute to sporadic AD.Source
J Neurochem. 2006 Feb;96(3):635-44. Epub 2005 Dec 20. Link to article on publisher's siteDOI
10.1111/j.1471-4159.2005.03552.xPermanent Link to this Item
http://hdl.handle.net/20.500.14038/25694PubMed ID
16371011Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1111/j.1471-4159.2005.03552.x