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Molecular Pharmacology

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Research ArticleArticle

Nordihydroguaiaretic Acid Affects Multiple Dynein-Dynactin Functions in Interphase and Mitotic Cells

Kohei Arasaki, Katsuko Tani, Tamotsu Yoshimori, David J. Stephens and Mitsuo Tagaya
Molecular Pharmacology February 2007, 71 (2) 454-460; DOI: https://doi.org/10.1124/mol.106.029611
Kohei Arasaki
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Katsuko Tani
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Tamotsu Yoshimori
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David J. Stephens
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Mitsuo Tagaya
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Abstract

Nordihydroguaiaretic acid (NDGA), a well known lipoxygenase inhibitor, actually has pleiotropic effects on cells, which include cell proliferation, apoptosis, differentiation, and chemotaxis. We and others have shown previously that this compound causes Golgi disassembly by an unknown mechanism. In this study, we show that, in parallel with Golgi disassembly, NDGA induces the accumulation of the microtubule minus-end-directed motor dynein-dynactin complex at the centrosome, where microtubules minus-ends lie. Concomitant with this accumulation, dynein-dynactin-interacting proteins, such as ZW10 and EB1, were also redistributed to the centrosomal region. In cells where microtubules were depolymerized by nocodazole, NDGA promoted the formation of filaments consisting of dynein-dynactin and its interacting proteins, suggesting that it stimulates the association of these proteins in an ordered, not random, manner. Loss of dynactin function abolished not only NDGA-induced redistribution in intact cells but also filament formation in nocodazole-treated cells. The latter finding implies that dynactin is a key molecule for the association between dynein-dynactin and its interacting proteins. In mitotic cells, NDGA induced robust accumulation of dyneindynactin and its interacting proteins at the spindle poles. These results taken together suggest that NDGA perturbs membrane traffic by affecting the function of the microtubule motor dynein-dynactin complex and its auxiliary proteins. To our knowledge, NDGA is the first case of a reagent that can modulate dynein-dynactin-related processes.

Footnotes

  • This work was supported in part by Grants-in-Aid for Scientific Research (16370089, 16044242, 16048229, and 16657309) from the Ministry of Education, Science, Sports and Culture of Japan. K.A. is a research fellow of the Japan Society for the Promotion of Science.

  • ABBREVIATIONS: NDGA, nordihydroguaiaretic acid; ER, endoplasmic reticulum; MT, microtubule; Ab, antibody; IC, intermediate chain; Noc, Nocodazole; DMSO, dimethyl sulfoxide; FITC, fluorescein isothiocyanate; Tf, Transferrin; TfR, Tf receptor.

    • Received August 4, 2006.
    • Accepted November 14, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 71 (2)
Molecular Pharmacology
Vol. 71, Issue 2
1 Feb 2007
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Research ArticleArticle

Nordihydroguaiaretic Acid Affects Multiple Dynein-Dynactin Functions in Interphase and Mitotic Cells

Kohei Arasaki, Katsuko Tani, Tamotsu Yoshimori, David J. Stephens and Mitsuo Tagaya
Molecular Pharmacology February 1, 2007, 71 (2) 454-460; DOI: https://doi.org/10.1124/mol.106.029611

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Research ArticleArticle

Nordihydroguaiaretic Acid Affects Multiple Dynein-Dynactin Functions in Interphase and Mitotic Cells

Kohei Arasaki, Katsuko Tani, Tamotsu Yoshimori, David J. Stephens and Mitsuo Tagaya
Molecular Pharmacology February 1, 2007, 71 (2) 454-460; DOI: https://doi.org/10.1124/mol.106.029611
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