THE JAWS MODEL OF TAU-MICROTUBULE INTERACTION EXAMINED IN CHO CELLS

Tau is a neuronal microtubule-associated protein which promotes microt ubule assembly. The C-terminal half of the protein contains three or f our tandem repeats that are often considered to be the microtubule bin ding 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 region s flanking the repeats are considered as targetting domains, responsib le for positioning tau on the microtubule surface, and the repeats whi ch act as catalytic domains for microtubule assembly, To examine wheth er this model is appropriate in vivo we generated recombinant tau isof orms and microinjected them into CHO cells, Immunofluorescence microsc opy of microtubules and tau shows that binding to microtubules, stabil ization of microtubules and formation of bundles is not achieved by ta u constructs comprising individual domains, but requires the combinati on of the flanking regions and the repeat domain, The results show tha t the jaws model describes the interactions between tau and microtubul es in living cells. Since the targetting and catalytic domains are aff ected differently by phosphorylation the model provides a basis for st udying the regulation of the interaction between microtubules and tau or other microtubule-associated proteins.