Tau Induces Ring and Microtubule Formation from -
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- 作者：Franç ; ois Devred ; Pascale Barbier ; Soazig Douillard ; Octavio Monasterio ; José ; Manuel Andreu ; and Vincent Peyrot
- 刊名：Biochemistry
- 出版年：2004
- 出版时间：August 17, 2004
- 年：2004
- 卷：43
- 期：32
- 页码：10520 - 10531
- 全文大小：261K
- 年卷期：v.43,no.32(August 17, 2004)
- ISSN：1520-4995
文摘
Tau is a neuronal microtubule-associated protein that plays a central role in many cellularprocesses, both physiological and pathological, such as axons stabilization and Alzheimer's disease. Despiteextensive studies, very little is known about the detailed molecular basis of tau binding to microtubules.We used the four-repeat recombinant htau40 and tubulin dimers to show for the first time that tau is ableto induce both microtubule and ring formation from 6S 
tubulin in phosphate buffer without addedmagnesium (nonassembly conditions). The amount of microtubules or rings formed was proteinconcentration-, temperature-, and nucleotide-dependent. By means of biophysical approaches, we showedthat tau binds to tubulin without global-folding change, detectable by circular dichroism. We alsodemonstrated that the tau-tubulin interaction follows a ligand-mediated elongation process, with twotau-binding site per tubulin dimer. Moreover, using a tubulin recombinant -tubulin C-terminal fragment(404-451) and a -tubulin C-terminal fragment (394-445), we demonstrated the involvement of both ofthese tubulin regions in tau binding. From this model system, we gain new insight into the mechanismsby which tau binds to tubulin and induces microtubule formation.
tubulin in phosphate buffer without addedmagnesium (nonassembly conditions). The amount of microtubules or rings formed was proteinconcentration-, temperature-, and nucleotide-dependent. By means of biophysical approaches, we showedthat tau binds to tubulin without global-folding change, detectable by circular dichroism. We alsodemonstrated that the tau-tubulin interaction follows a ligand-mediated elongation process, with twotau-binding site per tubulin dimer. Moreover, using a tubulin recombinant -tubulin C-terminal fragment(404-451) and a -tubulin C-terminal fragment (394-445), we demonstrated the involvement of both ofthese tubulin regions in tau binding. From this model system, we gain new insight into the mechanismsby which tau binds to tubulin and induces microtubule formation.