Publication List English

Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish

A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis

C3orf70 Is Involved in Neural and Neurobehavioral Development

Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation

Aging-associated microstructural deterioration of vertebra in zebrafish

tEGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase


Nature Communicationsvolume 9, Article number: 758 (2018)

Kousuke Kasahara, Hiromasa Aoki, Tohru Kiyono, Shujie Wang, Harumi Kagiwada, Mizuki Yuge, Toshio Tanaka, Yuhei Nishimura, Akira Mizoguchi, Naoki Goshima & Masaki Inagaki

Ciliogenesis is generally inhibited in dividing cells, however, it has been unclear which signaling cascades regulate the phenomenon. Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells. These phosphorylations elevate the deubiquitinase activity, which then stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through downregulation of the USP8-trichoplein-Aurora A signal. Moreover, primary cilia abrogation, which is induced upon IFT20 or Cep164 depletion, ameliorates the cell cycle arrest of EGFR knockdown cells. The present data reveal that the EGFR-USP8-trichoplein-Aurora A axis is a critical signaling cascade that restricts ciliogenesis in dividing cells, and functions to facilitate cell proliferation. We further show that usp8 knockout zebrafish develops ciliopathy-related phenotypes including cystic kidney, suggesting that USP8 is a regulator of ciliogenesis in vertebrates.


Nature Communications