SUBPOPULATIONS OF TAU INTERACT WITH MICROTUBULES AND ACTIN-FILAMENTS IN VARIOUS CELL-TYPES

It has been demonstrated that microtubule-associated proteins (MAPs) i nteract with tubulin in vitro and in vivo. However, there is no clear evidence on the possible roles of the interactions of MAPs in vivo wit h other cytoskeletal components in maintaining the integrity of the ce ll architecture. To address this question we extracted the neuronal cy toskeleton from brain cells and studied the selective dissociation of specific molecular isospecies of tau protein under various experimenta l conditions. Tau, and in some cases MAP-2, were analysed by the use o f anti-idiotypic antibodies that recognize epitopes on their tubulin b inding sites. Fractions of microtubule-bound tau isoforms were extract ed with 0.35 M NaCl or after the addition of nocodazole to allow micro tubule depolymerization. Protein eluted with this inhibitor contained most of the assembled tubulin dimer pool and part of the remaining tau and MAP-2. When the remaining cytoskeletal pellet was treated with cy tochalasin D to allow depolymerization of actin filaments, only tau is oforms were extracted. Immunoprecipitation studies along with immunolo calization experiments in cell lines containing tau-like components su pported the findings on the roles of tau isospecies as linkers between tubulin in the microtubular structure with actin filaments. Interesti ngly, in certain types of cells, antibody-reactive tau isospecies were detected by immunofluorescence with a discrete distribution pattern a long actin filaments, which was affected by cytochalasin disruption of the actin filament network. These results suggest the possible in viv o roles of subsets of tau protein in modulating the interactions betwe en microtubules and actin filaments.