FTDP‐17 mutations N279K and S305N in tau produce increased splicing of exon 10

FEBS Letters

Tabira, Takeshi³  Smith, Michael J²  Hasegawa, Masato²  Iijima, Masaaki¹  Goedert, Michel² 

[1] Department of Neuropsychiatry, Shimane Medical University, Izumo 693-8501, Japan;Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK;Division of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan

关键词: Tau protein mutation;    Microtubule assembly;    RNA splicing;    Frontotemporal dementia;   

DOI  :  10.1016/S0014-5793(98)01696-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Missense mutations and intronic mutations in the tau gene cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known missense mutations reduce the ability of tau to promote microtubule assembly. Intronic mutations lead to increased mRNA splicing of the alternatively spliced exon 10, resulting in an overproduction of tau isoforms with four microtubule-binding repeats. We show here that the recently identified FTDP-17 missense mutations N279K and S305N do not reduce the ability of tau to promote microtubule assembly. Instead they lead to increased splicing of exon 10, like the intronic mutations. The N279K and S305N mutations define a class of missense mutations in tau whose primary effects are at the RNA level.

【 授权许可】

Unknown