Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly.
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.
Hasegawa
M
M
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Smith
M J
MJ
Goedert
M
M
D019943:Amino Acid Substitution / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003704:Dementia / Q000235:genetics; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010300:Parkinson Disease / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D016875:tau Proteins / Q000235:genetics* / Q000502:physiology
D020033:Protein Isoforms; D016875:tau Proteins