Interactions of taxol, microtubule-associated proteins, and guanine nucleotides in tubulin polymerization.

Hamel, Ernest; Campo, A A del; Lowe, Michael C.; Lin, Chii M.

doi:10.1016/s0021-9258(19)68489-9

Cited by 107 publications

(50 citation statements)

References 25 publications

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“…However, the inhibition was incomplete and an effect on membrane integrity could not be excluded (44). In contrast to studying a microtubule-disrupting drug such as colchicine, this report describes the effect of taxol, which induces microtubule polymerization and stabilization (15,19,27,38,40). Surprisingly, depending on incubation conditions, taxol was found to either inhibit release of catecholamines after longterm incubation, or to provoke so-called spontaneous release…”

Section: Discussionmentioning

confidence: 89%

“…Taxol inhibits division of exponentially growing HeLa cells (38), blocks the replication of Trypanosoma cruzi (10), inhibits the migration behavior of mammalian fibroblast cells (31,39), and affects the morphology of PC j2 cells (14) and dorsal root ganglion and spinal cord neurons in cultures (30,32). The effects of taxol appear to be related to the tubulin-microtubule system (15,19,27,38,40). Taxol has the unusual capacity to promote assembly of microtubules in vitro, stabilizes microtubules against depolymerizing effects of low temperatures, and binds specifically to cellular microtubules.…”

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confidence: 99%

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Effect of taxol on secretory cells: functional, morphological, and electrophysiological correlates.

Thuret-Carnahan¹,

Bossu²,

Feltz³

et al. 1985

The Journal of Cell Biology

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The effect of 0.5-1.0 #M taxol, a potent promoter of microtubule polymerization in vitro, was studied on the secretory activity of chromaffin cells of the adrenal medulla. Taxol was found to have a dual effect: the long-term effect (after a 1-h incubation) of taxol was to induce almost complete inhibition of catecholamine release, whereas after a short incubation (10 rain) a massive, nicotine-independent release of catecholamine was produced. From results obtained using the patch-clamp technique to study the Ca+÷-dependent K ÷ channels (Ic channels), it was possible to conclude that taxol probably provokes an augmentation of free [Ca++]~ in the cytoplasm, values increasing from 10 -a M at rest to several 10 -7 M. The increased spontaneous release of stored neurohormones and the increased frequency of opening of Ic channels occur simultaneously and could both originate from a rise of [Ca++]~ upon taxol addition. Immunofluorescence and ultrastructural studies showed that 13-h taxol treatment of chromaffin cells led to a different distribution of secretory organelles, and also to microtubule reorganization. In treated cells, microtubules were found to form bundles beneath the cell membrane and, at the ultrastructural level, to be packed along the cell axis. It is concluded that in addition to its action on microtubules, the antitumor drug taxol has side effects on the cell secretory activity, one of them being to modify free [Ca++]i.

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

Effect of taxol on secretory cells: functional, morphological, and electrophysiological correlates.

Thuret-Carnahan¹,

Bossu²,

Feltz³

et al. 1985

The Journal of Cell Biology

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“…These include the absence of microtubule-associated proteins, 36S tubulincontaining ring structures, exogenously added guanosine 5' triphosphate, or organic buffer (27,50). Taxol induces microtubule assembly even at low temperatures (24,47,60). Microtubules assembled to steady state and then incubated with taxol become resistant to depolymerization by calcium, suggesting that there is a taxoi-binding site on the microtubule.…”

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confidence: 99%

Taxol binds to cellular microtubules.

Manfredi¹,

Parness²,

Horwitz³

1982

The Journal of Cell Biology

361

169

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ABSlRACT Taxol is a low molecular weight plant derivative which enhances microtubule assembly in vitro and has the unique ability to promote the formation of discrete microtubule bundles in cells. Tritium-labeled taxol binds directly to microtubules in vitro with a stoichiometry approaching one (Parness, J., and S. 8. Horwitz, 1981, J. Cell Biol. 91:479-487). We now report studies in cells on the binding of [aH]taxol and the formation of microtubule bundles.[aH]Taxol binds to the macrophagelike cell line, J774.2, in a specific and saturable manner. Scatchard analysis of the specific binding data demonstrates a single set of high affinity binding sites. Maximal binding occurs at drug concentrations which produce maximal growth inhibition. Conditions which depolymerize microtubles in intact and extracted cells as determined by tubulin immunofluorescence inhibit the binding of [aH]taxol. This strongly suggests that taxol binds specifically to cellular microtubules. Extraction with 0.1% Nonidet P-40 or depletion of cellular ATP by treatment with 10 mM NaNa prevents the characteristic taxol-induced bundle formation. The binding of [aH]taxol, however, is retained under these conditions. Thus, there must be specific cellular mechanisms which are required for bundle formation, in addition to the direct binding of taxol to cytoplasmic microtubules.Taxol, a novel diterpenoid, was originally isolated from the stem bark of the western yew, Taxus brevifolia, and has been found also in the leaves, stems and roots of a variety of other Taxus species (35,63). The drug is a complex ester, shown to be a taxane derivative containing a rare oxetan ring, and is the first compound of this type to have antileukemic and tumor inhibitory properties. Early work in our laboratory demonstrated that the drug inhibits replication of HeLa cells (47). Studies with P-388 cells taken from taxol-treated mice identified taxol as a mitotic spindle poison (22).Studies in vitro have shown that in marked contrast to other antimitotic drugs, taxol enhances both the rate and yield of microtubule assembly. The critical concentration of microtubule protein required for assembly is reduced, and the microtubules formed are stable to depolymerization by calcium or cold (47). Taxol also assembles tubulin under conditions in which polymerization would not normally occur. These include the absence of microtubule-associated proteins, 36S tubulincontaining ring structures, exogenously added guanosine 5' triphosphate, or organic buffer (27, 50). Taxol induces microtubule assembly even at low temperatures (24,47,60). Microtubules assembled to steady state and then incubated with taxol become resistant to depolymerization by calcium, suggesting that there is a taxoi-binding site on the microtubule. Maximal effects in vitro are seen at taxol concentrations stoichiometric with the tubulin dimer concentration (49). Recent work with [3H]taxol confirms that the drug does bind to the microtubule, and that such binding occurs with a stoichiometry approaching one (41).HeLa ...

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“…A cell‐based MT binding assay was used to elucidate the impact of these mutants on tau‐MT interactions. In this assay, Paclitaxel is added to promote MT polymerization and MT‐bound proteins can be separated from the supernatant by high speed centrifugation (Hamel et al., 1981; Vallee, 1982). The 0N4R isoform of WT tau without Paclitaxel was used as a negative control: a low amount of tau was found in the pellet with MTs and most of the tubulin is soluble in the supernatant (Figure 4a).…”

Section: Resultsmentioning

confidence: 99%

Pathogenic MAPT mutations Q336H and Q336R have isoform‐dependent differences in aggregation propensity and microtubule dysfunction

Xia

Nasif

2021

Journal of Neurochemistry

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The microtubule (MT)-associated protein tau can form pathological brain inclusions that define tauopathies, a group of heterogeneous neurological disorders that include both Alzheimer's disease and frontotemporal dementia, the two most common causes of dementia (Wang & Mandelkow, 2016). Genetic mutations in the MT-associated protein tau (MAPT) gene cause familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) (

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Interactions of taxol, microtubule-associated proteins, and guanine nucleotides in tubulin polymerization.

Cited by 107 publications

References 25 publications

Effect of taxol on secretory cells: functional, morphological, and electrophysiological correlates.

Effect of taxol on secretory cells: functional, morphological, and electrophysiological correlates.

Taxol binds to cellular microtubules.

Pathogenic MAPT mutations Q336H and Q336R have isoform‐dependent differences in aggregation propensity and microtubule dysfunction

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