Tau is a neuronal microtubule-associated protein which promotes microtubule assembly. The C-terminal half of the protein contains three or four tandem repeats that are often considered to be the microtubule binding domain. This view is in conflict with in vitro data showing that the repeat domain binds only weakly to microtubules while the domains flanking the repeats bind strongly, even in the absence of the repeats. This has lead us to propose a ‘jaws’ model of tau whereby the regions flanking the repeats are considered as targetting domains, responsible for positioning tau on the microtubule surface, and the repeats which act as catalytic domains for microtubule assembly. To examine whether this model is appropriate in vivo we generated recombinant tau isoforms and microinjected them into CHO cells. Immunofluorescence microscopy of microtubules and tau shows that binding to microtubules, stabilization of microtubules and formation of bundles is not achieved by tau constructs comprising individual domains, but requires the combination of the flanking regions and the repeat domain. The results show that the jaws model describes the interactions between tau and microtubules in living cells. Since the targetting and catalytic domains are affected differently by phosphorylation the model provides a basis for studying the regulation of the interaction between microtubules and tau or other microtubule-associated proteins.

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