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開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

DISC1/Neuregulin-1 and Schizophrenia

  • P1-364
  • 森 大輔 / Daisuke Mori:1,2,3 貝淵 弘三 / Kozo Kaibuchi:2 
  • 1:名古屋大学 脳とこころの研究センター / Brain & Mind Research Center, Nagoya University 2:名古屋大学・医・神経情報薬理学 / Pharmacology, Univ of Nagoya, Japan 3:名古屋大学・医・精神医学 / Psychiatry, Univ of Nagoya, Japan 

The schizophrenias have a lifetime prevalence of approximately 1% in the general population and give a serious and intractable mental disorder. It has not been still cleared the molecular mechanism of the schizophrenia onset to date. Recently, the assumption of the onset has been potentially confident of the developmental disability on central nervous system. Furthermore, schizophrenia is known to be multifactorial disease participating in not only a genetic factor but also an environmental factor during embryonic stage, perinatal stage, or adolescence. Many genomic analyses of schizophrenia patients have reported the candidate genes for onset risk of the symptom, resulting DISC1 is the most possible factor by the evidence of Scottish-descent analysis.
To elucidate the pathogenic mechanism of schizophrenia, we have analyzed DISC1 localization and function in neuronal cells. Our anti-DISC1 antibody enabled us to observe clear localization to Golgi apparatus in cultured neuron prepared from developing hippocampus. Previously, we have identified direct interaction of DISC1 and Neuregulin-1, which is a ligand of ErbB3 and ErbB4. To understand the sense of their association, we have attempted to develop a new experimental system that enables us to analyze the vesicles included with transmembrane proteins from Trans-Golgi network in a synclonized manner. In this presentation, our result using this system suggested that DISC1 was involved in regulating pro-Neuregulin-1 transport.
Here, we report that DISC1 interacts with intracellular domain of precursor pro-Neuregulin-1 (pro-NRG1) and regulates its secretion and then propose our hypothesis that DISC1 promotes the formation and budding of vesicles including DISC1-interacting proteins. For the more strict quantification of secretion, we developed a synchronized budding system of single-passed transmembrane protein through Golgi apparatus, and revealed that the budding of pro-NRG1 and the secretion of mature NRG1 were relatively impaired in full-length DISC1 deficient hippocampal neuron.

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