Taxol impairs anterograde axonal transport of microinjected horseradish peroxidase in dorsal root ganglia neurons in vitro

We have investigated the effects of taxol on the axonal transport of horser adish peroxidase (HRP) in dorsal root ganglia (DRG) cells and their neurona l cytoskeleton. The former were analysed by microinjection of HRP into sing le DRG cells and the latter was studied by means of immunohistochemistry an d cryo-electron microscopy. In cultured and untreated DRG cells, microinjec ted HRP was typically transported anterogradely several hundred micrometres along their neurites. Different exposure periods (1, 2 and 3 days) to taxo l were analysed. The axonal transport of HRP in DRG cells was time-dependen tly impeded by taxol. After the drug had been washed out, a recovery of the axonal transport of HRP was observed and confirmed by quantitative analysi s. Cryo-electron microscopy revealed an abnormal aggregation of axonal and cytoplasmic microtubules, associated with a decreased amount of cross-linki ng structures, in taxol-treated DRG cell cultures. After 3 days of taxol ex posure, microtubule-associated proteins and Tau-protein were restricted to the cellular somata but the neurofilament network and tubulin-proteins seem ed to be unaffected. Our results demonstrate, for the first time, an inhibi tion of anterograde axonal transport of HRP in single neurons by taxol. Thi s effect is reversible and seems not to be caused by cellular damage, but i s rather a consequence of an alterated organisation of microtubules and/or microtubule-associated proteins.