Fig. (2).

Coordination of substrate transport through the chaperone network. Upon stress induced microtubule disassembly, Hsp27 and perhaps other small Hsps, bind tau to prevent its toxic aggregation. The Hsp27/tau complex is stable, and tau can then be transferred to the Hsp70/DnaJ chaperone complex. If refolding is not possible, the tau-bound Hsp70 complex will associate with the Hsp90 complex for further attempts at refolding. Alternatively, the client is processed for degradation. The decisions are made based on coordinate regulation by the chaperones and cochaperones associating with the complex, such as Hsp90, CHIP and Hop.