Disrupted-In-Schizophrenia-1 (DISC1) regulates transport and translation of neuronal mRNA in hippocampal neurons

Disrupted-In-Schizophrenia 1 (DISC1) is one of the most promising susceptibility genes for major psychiatric disorders including schizophrenia and major depression. DISC1 is implicated in neuronal developments like neurogenesis, neuronal migration, axon/dendrite formation and synapse formation. We previously found that DISC1 links Kinesin-1 to Nudel/Lis1 and Grb2 and regulates their anterograde transport into axons of hippocampal neurons as a cargo adaptor (Taya et al, 2007). However, its modes of action remain largely unknown. Here, we comprehensively screened the DISC1-interacting proteins by combining affinity column and shot gun LC/MS/MS, and identified many RNA-binding proteins including Hzf, which acts as a component of RNA granules and participates in the dendritic transport of IP3 receptor 1 (IP3R1) mRNA DISC1 directly interacted with Hzf and co-localized with Hzf and RNA granules in hippocampal dendrites. DISC1 directly associated with IP3R1 mRNA and was co-transported into dendrites. The impairments of DISC1 functions prohibited dendritic transport and translation of IP3R1 mRNA Together, these results suggest that DISC1 together with Hzf interacts with a specific mRNAs such as IP3R1 mRNA and regulates their dendritic transport via Kinesin-1 and translation as a component of RNA granules.