Open Access

Phosphorylation of cortactin by cyclin-dependent kinase 5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells

  • Authors:
    • Tadashi Abe
    • The Mon La
    • Yuuzi Miyagaki
    • Eri Oya
    • Fan-Yan Wei
    • Kento Sumida
    • Kenshiro Fujise
    • Tetsuya Takeda
    • Kazuhito Tomizawa
    • Kohji Takei
    • Hiroshi Yamada
  • View Affiliations

  • Published online on: December 11, 2018     https://doi.org/10.3892/ijo.2018.4663
  • Pages: 550-558
  • Copyright: © Abe et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dynamin copolymerizes with cortactin to form a ring‑like complex that bundles and stabilizes actin filaments. Actin bundle formation is crucial for generation of filopodia and lamellipodia, which guide migration, invasion, and metastasis of cancer cells. However, it is unknown how the dynamin‑cortactin complex regulates actin bundle formation. The present study investigated phosphorylation of cortactin by cyclin‑dependent kinase 5 (CDK5) and its effect on actin bundle formation by the dynamin‑cortactin complex. CDK5 directly phosphorylated cortactin at T145/T219 in vitro. Phosphomimetic mutants in which one or both of these threonine residues was substituted by aspartate were used. The three phosphomimetic mutants (T145D, T219D and T145DT219D) had a decreased affinity for F‑actin. Furthermore, electron microscopy demonstrated that these phosphomimetic mutants could not form a ring‑like complex with dynamin 1. Consistently, the dynamin 1‑phosphomimetic cortactin complexes exhibited decreased actin‑bundling activity. Expression of the phosphomimetic mutants resulted in not only aberrant lamellipodia and short filopodia but also cell migration in NG108‑15 glioma‑derived cells. These results indicate that phosphorylation of cortactin by CDK5 regulates formation of lamellipodia and filopodia by modulating dynamin 1/cortactin‑dependent actin bundling. Taken together, these findings suggest that CDK5 is a potential molecular target for anticancer therapy.
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February-2019
Volume 54 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Abe T, La T, Miyagaki Y, Oya E, Wei F, Sumida K, Fujise K, Takeda T, Tomizawa K, Takei K, Takei K, et al: Phosphorylation of cortactin by cyclin-dependent kinase 5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells. Int J Oncol 54: 550-558, 2019
APA
Abe, T., La, T., Miyagaki, Y., Oya, E., Wei, F., Sumida, K. ... Yamada, H. (2019). Phosphorylation of cortactin by cyclin-dependent kinase 5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells. International Journal of Oncology, 54, 550-558. https://doi.org/10.3892/ijo.2018.4663
MLA
Abe, T., La, T., Miyagaki, Y., Oya, E., Wei, F., Sumida, K., Fujise, K., Takeda, T., Tomizawa, K., Takei, K., Yamada, H."Phosphorylation of cortactin by cyclin-dependent kinase 5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells". International Journal of Oncology 54.2 (2019): 550-558.
Chicago
Abe, T., La, T., Miyagaki, Y., Oya, E., Wei, F., Sumida, K., Fujise, K., Takeda, T., Tomizawa, K., Takei, K., Yamada, H."Phosphorylation of cortactin by cyclin-dependent kinase 5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells". International Journal of Oncology 54, no. 2 (2019): 550-558. https://doi.org/10.3892/ijo.2018.4663