Colchicine inhibition of microtubule assembly via copolymer formation

H. Sternlicht, I. Ringel

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114 Scopus citations

Abstract

Colchicine·tubulin complex (CD) inhibits microtubule assembly. The authors examined this inhibition under conditions where spontaneous nucleation was suppressed and assembly was restricted to an elongation polymerization. The authors found that CD inhibited assembly by a mechanism which preserved the ability of microtubule ends to add tubulin. This observation is inconsistent with the end-poisoning model which recently was proposed as a general mechanism for assembly inhibition by CD. The authors' data are consistent with the following model: (a) microtubules formed in the presence of CD are CD-tubulin copolymers: (b) these copolymers can have appreciable numbers of incorporated CDs which are most likely, randomly distributed in the copolymers; (c) CD-tubulin copolymers have assembly-competent ends with association and dissociation rate constants which decrease as the CD/tubulin ratio in the copolymers, (CD/T)(MT), increases; and (d) the critical tubulin concentrations required for microtubule assembly increase in the presence of CD, indicating that copolymer affinity for tubulin decreases as (CD/T)(MT) increases.

Original languageEnglish
Pages (from-to)10540-10550
Number of pages11
JournalJournal of Biological Chemistry
Volume254
Issue number20
StatePublished - 1979
Externally publishedYes

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