Paclitaxel induces axonal microtubules polar reconfiguration and impaired organelle transport: Implications for the pathogenesis of paclitaxel-induced polyneuropathy

Or A. Shemesh, Micha E. Spira

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

In differentiated axons almost all microtubules (MTs) uniformly point their plus ends towards the axonal tip. The uniform polar pattern provides the structural substrate for efficient organelle transport along axons. It is generally believed that the mass and pattern of MTs polar orientation remain unchanged in differentiated neurons. Here we examined long-term effects of the MTs stabilizing reagent paclitaxel (taxol) over MTs polar orientation and organelle transport in cultured Aplysia neurons. Unexpectedly, we found that rather than stabilizing the MTs, paclitaxel leads to their massive polar reconfiguration, accompanied by impaired organelle transport. Washout of paclitaxel does not lead to recovery of the polar orientation indicating that the new pattern is self-maintained. Taken together the data suggest that MTs in differentiated neurons maintain the potential to be reconfigured. Such reconfiguration may serve physiological functions or lead to degeneration. In addition, our observations offer a novel mechanism that could account for the development of peripheral neuropathy in patients receiving paclitaxel as an antitumor drug.

Original languageEnglish
Pages (from-to)235-248
Number of pages14
JournalActa Neuropathologica
Volume119
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Aplysia
  • Axoplasmic transport
  • Microtubules
  • Paclitaxel
  • Peripheral neuropathy
  • Plus ends binding proteins

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