The FTDP-17-linked mutation R406W abolishes the interaction of phosphorylated tau with microtubules.
The recent finding that several point mutations in the gene encoding for the microtubule-binding protein tau correlate with neurological disorders has heightened interest in the mechanisms of destabilization of this protein. In this study the functional consequences of the tau mutation R406W on the interaction of the protein with microtubules have been analyzed. Mutated tau is less phosphorylated than its normal counterpart at serines 396 and 404. Furthermore, the phosphorylated mutant protein is unable to bind to microtubules, and, as a consequence, microtubules assembled after transient nocodazole treatment in the presence of this tau variant contain only unmodified tau and appear to form more and longer bundles than those assembled in the presence of wild-type tau. We propose that phosphorylated tau, unbound to microtubules, could accumulate in the cytoplasm.
Pérez
M
M
Centro de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
Lim
F
F
Arrasate
M
M
Avila
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000235:genetics / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011485:Protein Binding / Q000502:physiology; D012694:Serine / Q000378:metabolism; D014162:Transfection; D014404:Tubulin / Q000032:analysis; D016875:tau Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000939:Epitopes; D014404:Tubulin; D016875:tau Proteins; D012694:Serine; D015739:Nocodazole