Title

Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases

UMMS Affiliation

Department of Cell Biology

Date

12-24-2004

Document Type

Article

Medical Subject Headings

*Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Brain; Gene Expression Regulation; Humans; Mice; Molecular Sequence Data; Neurodegenerative Diseases; Protein Isoforms; tau Proteins

Disciplines

Cell Biology

Abstract

Organization of cytoskeletal elements is critical for cellular migration and maintenance of morphology. Tau protein, which binds to and organizes microtubules, is instrumental in forming and maintaining the neuronal axon. Disturbances in tau expression result in disruption of the neuronal cytoskeleton and formation of pathological tau structures (neurofibrillary tangles, NFTs) found in brains of dementia sufferers. Null tau mice, although viable, exhibit developmental and cognitive defects and transgenic mice which overexpress tau develop severe neuropathies. The neuron-specific tau transcript produces multiple isoforms by intricately regulated alternative splicing. These isoforms modulate tau function in normal brain. Moreover, aberrations in tau splicing regulation directly cause several neurodegenerative diseases. Thus, tau splicing regulation is vital to neuronal health and correct brain function. This review briefly presents our cumulative knowledge of tau splicing-cis elements and trans factors which influence it at the RNA level, its effect on the structure and roles of the tau protein and its repercussions on neuronal morphology and neurodegeneration.

Rights and Permissions

Citation: Biochim Biophys Acta. 2005 Jan 3;1739(2-3):91-103. Link to article on publisher's site

Related Resources

Link to Article in PubMed