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Article 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

Corrigendum in: /10.3892/ijo.2020.4962
  • 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 / Copyright

    Affiliations: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan, Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
    Copyright: © Abe et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 550-558
    |
    Published online on: December 11, 2018
       https://doi.org/10.3892/ijo.2018.4663
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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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1 

Arjonen A, Kaukonen R and Ivaska J: Filopodia and adhesion in cancer cell motility. Cell Adhes Migr. 5:421–430. 2011. View Article : Google Scholar

2 

Ridley AJ: Life at the leading edge. Cell. 145:1012–1022. 2011. View Article : Google Scholar

3 

MacGrath SM and Koleske AJ: Cortactin in cell migration and cancer at a glance. J Cell Sci. 125:1621–1626. 2012. View Article : Google Scholar : PubMed/NCBI

4 

McNiven MA, Kim L, Krueger EW, Orth JD, Cao H and Wong TW: Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape. J Cell Biol. 151:187–198. 2000. View Article : Google Scholar

5 

Yamada H, Abe T, Satoh A, Okazaki N, Tago S, Kobayashi K, Yoshida Y, Oda Y, Watanabe M, Tomizawa K, et al: Stabilization of actin bundles by a dynamin 1/cortactin ring complex is necessary for growth cone filopodia. J Neurosci. 33:4514–4526. 2013. View Article : Google Scholar

6 

Yamada H, Takeda T, Michiue H, Abe T and Takei K: Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells. Int J Oncol. 49:877–886. 2016. View Article : Google Scholar

7 

Weaver AM, Heuser JE, Karginov AV, Lee WL, Parsons JT and Cooper JA: Interaction of cortactin and N-WASp with Arp2/3 complex. Curr Biol. 12:1270–1278. 2002. View Article : Google Scholar

8 

Kinley AW, Weed SA, Weaver AM, Karginov AV, Bissonette E, Cooper JA and Parsons JT: Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion. Curr Biol. 13:384–393. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Contreras-Vallejos E, Utreras E and Gonzalez-Billault C: Going out of the brain: Non-nervous system physiological and pathological functions of Cdk5. Cell Signal. 24:44–52. 2012. View Article : Google Scholar

10 

Nikolic M, Dudek H, Kwon YT, Ramos YF and Tsai LH: The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev. 10:816–825. 1996. View Article : Google Scholar

11 

Liu KC, Leuckx G, Sakano D, Seymour PA, Mattsson CL, Rautio L, Staels W, Verdonck Y, Serup P, Kume S, et al: Inhibition of Cdk5 Promotes β-Cell Differentiation From Ductal Progenitors. Diabetes. 67:58–70. 2018. View Article : Google Scholar

12 

Pozo K and Bibb JA: The emerging role of Cdk5 in cancer. Trends Cancer. 2:606–618. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Quintavalle M, Elia L, Price JH, Heynen-Genel S and Courtneidge SA: A cell-based high-content screening assay reveals activators and inhibitors of cancer cell invasion. Sci Signal. 4:ra492011. View Article : Google Scholar

14 

Feldmann G, Mishra A, Hong SM, Bisht S, Strock CJ, Ball DW, Goggins M, Maitra A and Nelkin BD: Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling. Cancer Res. 70:4460–4469. 2010. View Article : Google Scholar

15 

Yamada H, Kikuchi T, Masumoto T, Wei FY, Abe T, Takeda T, Nishiki T, Tomizawa K, Watanabe M, Matsui H, et al: Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone. Biol Cell. 107:319–330. 2015. View Article : Google Scholar

16 

Tan TC, Valova VA, Malladi CS, Graham ME, Berven LA, Jupp OJ, Hansra G, McClure SJ, Sarcevic B, Boadle RA, et al: Cdk5 is essential for synaptic vesicle endocytosis. Nat Cell Biol. 5:701–710. 2003. View Article : Google Scholar

17 

Tomizawa K, Sunada S, Lu YF, Oda Y, Kinuta M, Ohshima T, Saito T, Wei FY, Matsushita M, Li ST, et al: Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. J Cell Biol. 163:813–824. 2003. View Article : Google Scholar

18 

Schafer DA, Weed SA, Binns D, Karginov AV, Parsons JT and Cooper JA: Dynamin2 and cortactin regulate actin assembly and filament organization. Curr Biol. 12:1852–1857. 2002. View Article : Google Scholar

19 

Nozumi M, Nakagawa H, Miki H, Takenawa T and Miyamoto S: Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone. J Cell Sci. 116:239–246. 2003. View Article : Google Scholar

20 

Jeannot P and Besson A: Cortactin function in invadopodia. Small GTPases. Dec 31–2017.Epub ahead of print. View Article : Google Scholar

21 

Wong AS, Lee RH, Cheung AY, Yeung PK, Chung SK, Cheung ZH and Ip NY: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson’s disease. Nat Cell Biol. 13:568–579. 2011. View Article : Google Scholar

22 

Liang S, Wei FY, Wu YM, Tanabe K, Abe T, Oda Y, Yoshida Y, Yamada H, Matsui H, Tomizawa K, et al: Major Cdk5-dependent phosphorylation sites of amphiphysin 1 are implicated in the regulation of the membrane binding and endocytosis. J Neurochem. 102:1466–1476. 2007. View Article : Google Scholar

23 

Moutal A, Villa LS, Yeon SK, Householder KT, Park KD, Sirianni RW and Khanna R: CRMP2 Phosphorylation Drives Glioblastoma Cell Proliferation. Mol Neurobiol. 55:4403–4416. 2018.

24 

Liu R, Tian B, Gearing M, Hunter S, Ye K and Mao Z: Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion. Proc Natl Acad Sci USA. 105:7570–7575. 2008. View Article : Google Scholar

25 

Yushan R, Wenjie C, Suning H, Yiwu D, Tengfei Z, Madushi WM, Feifei L, Changwen Z, Xin W, Roodrajeetsing G, et al: Insights into the clinical value of cyclin-dependent kinase 5 in glioma: A retrospective study. World J Surg Oncol. 13:2232015. View Article : Google Scholar

26 

Martin KH, Jeffery ED, Grigera PR, Shabanowitz J, Hunt DF and Parsons JT: Cortactin phosphorylation sites mapped by mass spectrometry. J Cell Sci. 119:2851–2853. 2006. View Article : Google Scholar

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Copy and paste a formatted citation
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 Corrigendum in /10.3892/ijo.2020.4962. 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 Corrigendum in /10.3892/ijo.2020.4962. 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 Corrigendum in /10.3892/ijo.2020.4962". 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 Corrigendum in /10.3892/ijo.2020.4962". International Journal of Oncology 54, no. 2 (2019): 550-558. https://doi.org/10.3892/ijo.2018.4663
Copy and paste a formatted citation
x
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 Corrigendum in /10.3892/ijo.2020.4962. 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 Corrigendum in /10.3892/ijo.2020.4962. 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 Corrigendum in /10.3892/ijo.2020.4962". 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 Corrigendum in /10.3892/ijo.2020.4962". International Journal of Oncology 54, no. 2 (2019): 550-558. https://doi.org/10.3892/ijo.2018.4663
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