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

• Published in: FEBS letters Vol. 461; no. 1; pp. 91 - 95
• Main Authors: Yen, Samuel, Easson, Colin, Nacharaju, Parimala, Hutton, Michael, Yen, Shu-Hui
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 12.11.1999
• Subjects: Calpain - metabolism; Calpain I; Chromosome 17; Chromosomes, Human, Pair 17; Dementia - genetics; Frontal Lobe - pathology; Frontal temporal dementia; Humans; Immunoblotting; Kinetics; Mutation; Parkinsonian Disorders - genetics; Parkinsonism; Recombinant Proteins - metabolism; Silver Staining; Tau gene; tau Proteins - genetics; Time Factors; Parkinsonism; Frontal temporal dementia; Tau gene; Chromosome 17; Calpain I
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)01427-1

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.