FTDP‐17 tau mutations decrease the susceptibility of tau to calpain I digestion

FEBS Letters

Hutton, Michael¹  Nacharaju, Parimala¹  Yen, Samuel¹  Yen, Shu-Hui¹  Easson, Colin¹ 

[1] Department of Pharmacology, Birdsall Medical Research Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA

关键词: Frontal temporal dementia;    Parkinsonism;    Chromosome 17;    Tau gene;    Calpain I;   

DOI  :  10.1016/S0014-5793(99)01427-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation.

【 授权许可】

Unknown