DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2

Tomoyasu Shinoda, Shinichiro Taya, Daisuke Tsuboi, Takao Hikita, Reiko Matsuzawa, Setsuko Kuroda, Akihiro Iwamatsu, Kozo Kaibuchi

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Abstract

Disrupted-in-Schizophrenia-1 (DISC1) is a candidate gene for susceptibility of schizophrenia. In the accompanying paper (Taya et al., 2006), we report that DISC1 acts as a linker between Kinesin-1 and DISC1-interacting molecules, such as NudE-like, lissencephaly-1, and 14-3-3ε. Here we identified growth factor receptor bound protein 2 (Grb2) as a novel DISC1-interacting molecule. Grb2 acts as an adaptor molecule that links receptor tyrosine kinases and the Ras-extracellular signal-regulated kinase (ERK) pathway. DISC1 formed a ternary complex with Grb2 and kinesin heavy chain KIF5A of Kinesin-1. In cultured rat hippocampal neurons, both DISC1 and Grb2 partially colocalized at the distal part of axons. Knockdown of DISC1 or kinesin light chains of Kinesin-1 by RNA interference inhibited the accumulation of Grb2 from the distal part of axons. Knockdown of DISC1 also inhibited the neurotrophin-3 (NT-3)-induced phosphorylation of ERK-1/2 at the distal part of axons and inhibited NT-3-induced axon elongation. These results suggest that DISC1 is required for NT-3-induced axon elongation and ERK activation at the distal part of axons by recruiting Grb2 to axonal tips.

Original languageEnglish
Pages (from-to)4-14
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number1
DOIs
Publication statusPublished - 03-01-2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Shinoda, T., Taya, S., Tsuboi, D., Hikita, T., Matsuzawa, R., Kuroda, S., Iwamatsu, A., & Kaibuchi, K. (2007). DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. Journal of Neuroscience, 27(1), 4-14. https://doi.org/10.1523/JNEUROSCI.3825-06.2007