Effect of alkaline pH on taxol-microtubule interactions

I. Ringel, S. B. Horwitz

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Taxol stabilizes microtubules against the depolymerizing effects of cold temperature, drugs and Ca++. In this report, the effect of alkaline pH on microtubules polymerized in the presence of taxol has been studied. Although taxol-microtubules are more stable than microtubules assembled in the presence of GTP, taxol-microtubules can be partially disassembled when the pH becomes more alkaline. A portion of the recovered tubulin dimer is assembly competent upon pH adjustment to ~6.6 and the microtubules formed upon the induction of assembly by GTP are normal as judged by electron microscopy. The data indicate that alkaline pH can be used to recover assembly-competent tubulin from a taxol-microtubule complex. At pH 6.6, taxol-induced polymers consisted of two components. The majority were microtubules, but in addition hoops and ribbons were also present. At alkaline pH, the microtubules were more stable than the hoops and ribbons and at pH > 7.5 they were the only stable structures. Microtubules stabilized by taxol are protected against the depolymerizing action of podophyllotoxin even at alkaline pH, whereas the hoops and ribbons are depolymerized.

Original languageEnglish (US)
Pages (from-to)855-860
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume259
Issue number2
StatePublished - Dec 1 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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