DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of lisl and DISCI through control of Ndell dual-phosphorylation

Masayuki Okamoto, Tokuichi Iguchi, Tsuyoshi Hattori, Shinsuke Matsuzaki, Yoshihisa Koyama, Manabu Taniguchi, Munekazu Komada, Min Jue Xie, Hideshi Yagi, Shoko Shimizu, Yoshiyuki Konishi, Minoru Omi, Tomohiko Yoshimi, Taro Tachibana, Shigeharu Fujieda, Taiichi Katayama, Akira Ito, Shinji Hirotsune, Masaya Tohyama, Makoto Sato

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cell positioning and neuronal network formation are crucial for proper brain function. Disrupted-in-Schizophrenia 1 (DISCI) is antero-gradely transported to the neurite tips, together with Lisl, and functions in neurite extension via suppression of GSK313 activity. Then, transported Lisl is retrogradely transported and functions in cell migration. Here, we showthat DISCl-binding zinc fingerprotein (DBZ), together with DISCl, regulates mouse cortical cell positioning and neurite development in vivo. DBZ hindered Ndell phosphorylation at threonine 2l9 and serine 25l. DBZ depletion or expression of a double-phosphorylated mimetic form of Ndell impaired the transport of Lisl and DISCl to the neurite tips and hampered microtubule elongation. Moreover, application of DISCl or a GSK313 inhibitor rescued the impairments caused by DBZ insufficiency or double-phosphorylated Ndell expression. We concluded that DBZ controls cell positioning and neurite development by interfering with Ndell from disproportionate phosphorylation, which is critical for appropriate anterograde transport of the DISCl-complex.

Original languageEnglish
Pages (from-to)2942-2958
Number of pages17
JournalJournal of Neuroscience
Volume35
Issue number7
DOIs
Publication statusPublished - 18-02-2015

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Okamoto, M., Iguchi, T., Hattori, T., Matsuzaki, S., Koyama, Y., Taniguchi, M., Komada, M., Xie, M. J., Yagi, H., Shimizu, S., Konishi, Y., Omi, M., Yoshimi, T., Tachibana, T., Fujieda, S., Katayama, T., Ito, A., Hirotsune, S., Tohyama, M., & Sato, M. (2015). DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of lisl and DISCI through control of Ndell dual-phosphorylation. Journal of Neuroscience, 35(7), 2942-2958. https://doi.org/10.1523/JNEUROSCI.5029-13.2015