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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

DISC1 regulates neurotrophin- induced axon elongation via interaction with Grb2.

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 14-3-3epsilon. 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.[1]


  1. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. Shinoda, T., Taya, S., Tsuboi, D., Hikita, T., Matsuzawa, R., Kuroda, S., Iwamatsu, A., Kaibuchi, K. J. Neurosci. (2007) [Pubmed]
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