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Research ArticleArticle

Staurosporine Induces Formation of Two Types of Extra-Long Cell Protrusions: Actin-Based Filaments and Microtubule-Based Shafts

Takayuki Kohno, Takafumi Ninomiya, Shin Kikuchi, Takumi Konno and Takashi Kojima
Molecular Pharmacology May 2015, 87 (5) 815-824; DOI: https://doi.org/10.1124/mol.114.096982
Takayuki Kohno
Department of Cell Science, Research Institute for Frontier Medicine (T.Koh., T.Kon., T.Koj.), and Department of Anatomy, Sapporo Medical University, Sapporo, Japan (T.N., S.K.)
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Takafumi Ninomiya
Department of Cell Science, Research Institute for Frontier Medicine (T.Koh., T.Kon., T.Koj.), and Department of Anatomy, Sapporo Medical University, Sapporo, Japan (T.N., S.K.)
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Shin Kikuchi
Department of Cell Science, Research Institute for Frontier Medicine (T.Koh., T.Kon., T.Koj.), and Department of Anatomy, Sapporo Medical University, Sapporo, Japan (T.N., S.K.)
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Takumi Konno
Department of Cell Science, Research Institute for Frontier Medicine (T.Koh., T.Kon., T.Koj.), and Department of Anatomy, Sapporo Medical University, Sapporo, Japan (T.N., S.K.)
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Takashi Kojima
Department of Cell Science, Research Institute for Frontier Medicine (T.Koh., T.Kon., T.Koj.), and Department of Anatomy, Sapporo Medical University, Sapporo, Japan (T.N., S.K.)
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Abstract

Staurosporine (STS) has been known as a classic protein kinase C inhibitor and is a broad-spectrum inhibitor targeting over 250 protein kinases. In this study, we observed that STS treatment induced drastic morphologic changes, such as elongation of a very large number of nonbranched, actin-based long cell protrusions that reached up to 30 µm in an hour without caspase activation or PARP cleavage in fibroblasts and epithelial cells. These cell protrusions were elongated not only from the free cell edge but also from the cell-cell junctions. The elongation of STS-dependent protrusions was required for ATP hydrolysis and was dependent on myosin-X and fascin but independent of Cdc42 and VASP. Interestingly, in the presence of an actin polymerization inhibitor, namely, cytochalasin D, latrunculin A, or jasplakinolide, STS treatment induced excess tubulin polymerization, which resulted in the formation of many extra-long microtubule (MT)–based protrusions toward the outside of the cell. The unique MT-based protrusions were thick and linear compared with the STS-induced filaments or stationary filopodia. These protrusions, which were composed of microtubules, have been scarcely observed in cultured non-neuronal cells. Taken together, our findings revealed that STS-sensitive kinases are essential for the maintenance of normal cell morphology, and a common unidentified molecular mechanism is involved in the formation of the following two different types of protrusions: actin-based filaments and MT-based shafts.

Footnotes

    • Received November 19, 2014.
    • Accepted February 13, 2015.
  • This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The authors declare no competing financial interests.

  • dx.doi.org/10.1124/mol.114.096982.

  • ↵Embedded ImageThis article has supplemental material available at molpharm.aspetjournals.org.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 87 (5)
Molecular Pharmacology
Vol. 87, Issue 5
1 May 2015
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Research ArticleArticle

Staurosporine Extends Two Types of Extra-Long Protrusions

Takayuki Kohno, Takafumi Ninomiya, Shin Kikuchi, Takumi Konno and Takashi Kojima
Molecular Pharmacology May 1, 2015, 87 (5) 815-824; DOI: https://doi.org/10.1124/mol.114.096982

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Research ArticleArticle

Staurosporine Extends Two Types of Extra-Long Protrusions

Takayuki Kohno, Takafumi Ninomiya, Shin Kikuchi, Takumi Konno and Takashi Kojima
Molecular Pharmacology May 1, 2015, 87 (5) 815-824; DOI: https://doi.org/10.1124/mol.114.096982
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