Tau proteins with FTDP‐17 mutations have a reduced ability to promote microtubule assembly

It is reported here that the G272V, P301L, V337M and R406W mutations lead to a marked reduction in the ability of tau to promote microtubule assembly, suggesting partial loss‐of‐function may be the primary effect of the known missense mutations in tau.

Abstract

Recently exonic and intronic mutations in the gene for microtubule-associated protein tau have been discovered in cases of familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Intronic mutations have been shown to lead to an abnormal preponderance of four-repeat tau isoforms. The effects of the exonic mutations are unknown. We report here that the G272V, P301L, V337M and R406W mutations lead to a marked reduction in the ability of tau to promote microtubule assembly. This partial loss-of-function may be the primary effect of the known missense mutations in tau.