研究者詳細 - 篠田　友靖

Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation 査読有り

Ito Hidenori, Morishita Rika, Shinoda Tomoyasu, Sudo Kaori, Iwamoto Ikuko, Nagata Koh-ichi

NEUROSCIENCE RESEARCH 68 巻頁： E120 - E120 2010年

Septin 14 is involved in cortical neuronal migration via interaction with Septin 4 査読有り

Shinoda Tomoyasu, Ito Hidenori, Sudo Kaori, Iwamoto Ikuko, Morishita Rika, Nagata Koh-ichi

NEUROSCIENCE RESEARCH 68 巻頁： E251 - E251 2010年

Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein 査読有り

Hikita, T; Taya, S; Fujino, Y; Taneichi-Kuroda, S; Ohta, K; Tsuboi, D; Shinoda, T; Kuroda, K; Funahashi, Y; Uraguchi-Asaki, J; Hashimoto, R; Kaibuchi, K

JOURNAL OF NEUROCHEMISTRY 110 巻 ( 5 ) 頁： 1567 - 1574 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neurochemistry

Schizophrenia is a complex mental disorder with fairly high level of heritability. Dystrobrevin binding protein 1, a gene encoding dysbindin protein, is a susceptibility gene for schizophrenia that was identified by family-based association analysis. Recent studies revealed that dysbindin is involved in the exocytosis and/or formation of synaptic vesicles. However, the molecular function of dysbindin in synaptic transmission is largely unknown. To investigate the signaling pathway in which dysbindin is involved, we isolated dysbindin-interacting molecules from rat brain lysate by combining ammonium sulfate precipitation and dysbindin-affinity column chromatography, and identified dysbindin-interacting proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Proteins involved in protein localization process, including Munc18-1, were identified as dysbindin-interacting proteins. Munc18-1 was co-immunoprecipitated with dysbindin from rat brain lysate, and directly interacted with dysbindin in vitro. In primary cultured rat hippocampal neurons, a part of dysbindin was co-localized with Munc18-1 at pre-synaptic terminals. Our result suggests a role for dysbindin in synaptic vesicle exocytosis via interaction with Munc18-1. © 2009 The Authors.

DOI： 10.1111/j.1471-4159.2009.06257.x

Sept14 is involved in the proper positioning of cortical pyramidal neuron 査読有り

Shinoda Tomoyasu, Ito Hidenori, Sudo Kaori, Iwamoto Ikuko, Morishita Rika, Nagata Koh-Ichi

NEUROSCIENCE RESEARCH 65 巻頁： S94 - S94 2009年

DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2 査読有り

Shinoda, T; Taya, S; Tsuboi, D; Hikita, T; Matsuzawa, R; Kuroda, S; Iwamatsu, A; Kaibuchi, K

JOURNAL OF NEUROSCIENCE 27 巻 ( 1 ) 頁： 4 - 14 2007年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neuroscience

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. Copyright © 2007 Society for Neuroscience.

DOI： 10.1523/JNEUROSCI.3825-06.2007

DISC1 regulates the transport of the NUDEL/LIS1/14-3-3ε complex through Kinesin-1 査読有り

Taya, S; Shinoda, T; Tsuboi, D; Asaki, J; Nagai, K; Hikita, T; Kuroda, S; Kuroda, K; Shimizu, M; Hirotsune, S; Iwamatsu, A; Kaibuchi, K

JOURNAL OF NEUROSCIENCE 27 巻 ( 1 ) 頁： 15 - 26 2007年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neuroscience

Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. Although the functional significance of this complex in neuronal development has been reported, the transport mechanism of the complex into axons and their functions in axon formation remain essentially unknown. Here we report that Kinesin-1, a motor protein of anterograde axonal transport, was identified as a novel DISC1-interacting molecule. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3ε complex through DISC1, and these molecules localized mainly at cell bodies and partially in the distal part of the axons. DISC1 partially colocalized with Kinesin family member 5A, NUDEL, LIS1, and 14-3-3ε in the growth cones. The knockdown of DISC1 by RNA interference or the dominant-negative form of DISC1 inhibited the accumulation of NUDEL, LIS1, and 14-3-3ε at the axons and axon elongation. The knockdown or the dominant-negative form of Kinesin-1 inhibited the accumulation of DISC1 at the axons and axon elongation. Furthermore, the knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3ε complex into the axons as a cargo receptor for axon elongation. Copyright © 2007 Society for Neuroscience.

DOI： 10.1523/JNEUROSCI.3826-06.2006

Plexin-A4 mediates axon-repulsive activities of both secreted and transmembrane semaphorins and plays roles in nerve fiber guidance 査読有り

DISC1 interacts with RNA-binding proteins in messenger ribonucleoprotein complex 査読有り

Tsuboi D, Taya S, Shinoda T, Hikita T, Kuroda S, Kaibuchi K

JOURNAL OF PHARMACOLOGICAL SCIENCES 100 巻頁： 242P - 242P 2006年

Suto F, Ito K, Uemura M, Shimizu M, Shinkawa Y, Sanbo M, Shinoda T, Tsuboi M, Takashima S, Yagi T, Fujisawa H

JOURNAL OF NEUROSCIENCE 25 巻 ( 14 ) 頁： 3628 - 3637 2005年4月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neuroscience

It has been proposed that four members of the plexin A subfamily (plexin-As; plexin-A1, -A2, -A3, and -A4) and two neuropilins (neuropilin-1 and neuropilin-2) form complexes and serve as receptors for class 3 secreted semaphorins (Semas), potent neural chemorepellents. The roles of given plexin-A4 in semaphorin signaling and axon guidance, however, are mostly unknown. Here, to elucidate functions of plexin-A4 in semaphorin signaling and axon guidance events in vivo, we generated plexin-A4 null mutant mice by targeted disruption of the plexin-A4 gene. Plexin-A4 mutant mice were defective in the trajectory and projection of peripheral sensory axons and sympathetic ganglion (SG) axons and the formation of the anterior commissure and the barrels. The defects in peripheral sensory and SG axons were fundamentally related to those of neuropilin-1 or Sema3A mutant embryos reported but were more moderate than the phenotype in these mutants. The growth cone collapse assay showed that dorsal root ganglion axons and SG axons of plexin-A4 mutant embryos partially lost their responsiveness to Sema3A. These results suggest that plexin-A4 plays roles in the propagation of Sema3A activities and regulation of axon guidance and that other members of the plexin-A subfamily are also involved in the propagation of Sema3A activities. Plexin-A4-deficient SG axons did not lose their responsiveness to Sema3F, suggesting that plexin-A4 serves as a Sema3A-specific receptor, at least in SG axons. In addition, the present study showed that plexin-A4 bound class 6 transmembrane semaphorins, Sema6A and Sema6B, and mediated their axon-repulsive activities, independently of neuropilin-1. Our results imply that plexin-A4 mediates multiple semaphorin signals and regulates axon guidance in vivo. Copyright © 2005 Society for Neuroscience.

DOI： 10.1523/JNEUROSCI.4480-04.2005