Functional analysis of the BRAG3-Arf6 pathway in the inhibitory synapse

2013 Fiscal Year Final Research Report

• Project/Area Number: 22300114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kitasato University
• Principal Investigator: SAKAGAMI Hiroyuki 北里大学, 医学部, 教授 (90261528)
• Co-Investigator(Renkei-kenkyūsha): TAMAKI Hideaki 北里大学, 医学部, 講師 (30155246) ; HARA Yoshinobu 北里大学, 医学部, 助教 (40558467)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 抑制性シナプス / 低分子量GTP結合タンパク質 / シナプス後肥厚部

Research Abstract

The aim of this study is to provide anatomincal evidence for the BRAG3-Arf6 pathway as a novel regulator of membrane traffic and actin cytoskeleton in the inhibitory synapse. First, we immunohistochemically demonstrated that BRAG3 localizes preferentially at postsynaptic specializations of symmetric synapses. Using yeast two-hybrid and pull down assays, we identified that BRAG3 can interact with utrophin/dystrophin and S-SCAM/MAGI-2, scaffolding proteins that localize at inhibitory synapses. Taken together, these findings suggest that BRAG3 may regulate the membrane traffic and actin cytoskeleton at inhibitory synapses through the interaction with scaffold proteins such as dystrophin and S-SCAM.

Research Products

• [Journal Article] CaMKII activity is essential for improvement of memory-related behavior by chronic rivastigmine treatment (2014)
  • Author(s): Moriguchi S, Tagashira H, Sasaki Y, Yeh JZ, Sakagami H, Narahashi T, Fukunaga K
  • Journal Title: J. Neurochem Volume: 128 Pages: 927-937
  • DOI: 10.1111/jnc.12510
  • Peer Reviewed
• [Journal Article] EFA6A, a gunanine nucleotide exchange factor for Arf6, interacts with sorting nexin-1 and regulates neurite outgrowth (2014)
  • Author(s): Fukaya M, Fukushima D, Hara Y, Sakagami H
  • Journal Title: J. Neurochem Volume: 129 Pages: 21-36
  • DOI: 10.1111/jnc.12524
  • Peer Reviewed
• [Journal Article] Endosomal localization of FIP3/Arfophilin-1 and its involvement in dendritic formation of mouse hippocampal neurons (2014)
  • Author(s): Yazaki Y, Hara Y, Tamaki H, Fukaya M, Sakagami H
  • Journal Title: Brain Res Volume: 1557 Pages: 55-65
  • DOI: 10.1016/j.brainres.2014
  • Peer Reviewed
• [Journal Article] Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina (2013)
  • Author(s): Sakagami H, Katsumata O, Hara Y, Tamaki H, Watanabe M, Harvey RJ, Fukaya M
  • Journal Title: J. Comp. Neurol Volume: 521 Pages: 860-876
  • DOI: 10.1002/cne.23206
  • Peer Reviewed
• [Journal Article] Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment (2013)
  • Author(s): Song N, Nakagawa S, Izumi T, Toda H, Kato A, Boku S, Inoue T, Sakagami H, Li X, Koyama T
  • Journal Title: Int J Neuropsychopharmacol Volume: 16(4) Pages: 803-812
  • DOI: 10.1017/S1461145712000570
  • Peer Reviewed
• [Journal Article] EFA6 activates Arf6 and participates in its targeting to the Flemming body during cytokinesis (2013)
  • Author(s): Ueda T, Hanai A, Takei T, Kubo K, Ohgi M, Sakagami H, Takahashi S, Shin HW, Nakayama K
  • Journal Title: FEBS Lett Volume: 583 Pages: 1617-1623
  • DOI: 10.1016/j.febslet.2013.03.042
  • Peer Reviewed
• [Journal Article] Type I phosphatidylinositol 4-phosphate 5-kinase γ is required for neuronal migration in the mouse developing cerebral cortex (2013)
  • Author(s): Hara Y, Fukaya M, Tamaki H, Sakagami H
  • Journal Title: Eur. J. Neurosci Volume: 38 Pages: 2659-2671
  • DOI: 10.1111/ejn.12286
  • Peer Reviewed
• [Journal Article] Inducible and Conditional Deletion of Extracellular Signal-regulated Kinase 5 Disrupts Adult Hippocampal Neurogenesis (2012)
  • Author(s): Pan YW, Zou J, Wang W, Sakagami H, Garelick MG, Abel G, Kuo CT, Storm DR, Xia Z
  • Journal Title: J Biol Chem Volume: 287(28) Pages: 23306-23317
  • DOI: 10.1074/jbc.M112.344762
  • Peer Reviewed
• [Journal Article] Pilt is a coiled-coil domain-containing protein that localizes at the trans-Golgi complex and regulates its structure (2012)
  • Author(s): Tamaki H, Sanda M, Katsumata O, Hara Y, Fukaya M, Sakagami H
  • Journal Title: FEBS Lett Volume: 586 Pages: 3064-3070
  • DOI: 10.1016/j.febslet.2012.07.051
  • Peer Reviewed
• [Journal Article] Accumulation of a-synuclein triggered by presynaptic dysfunction (2012)
  • Author(s): Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H, Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H
  • Journal Title: J. Neurosci Volume: 32 Pages: 17186-17196
  • DOI: 10.1523/JNEUROSCI.2220-12.2012
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent protein kinases in the carotid body : an immunohistochemical study (2012)
  • Author(s): Pokorski M, Sakagami H, Okada Y
  • Journal Title: Springerplus Volume: 1 Pages: 16
  • DOI: 10.1186/2193-1801-1-16.eCollection2012
  • Peer Reviewed
• [Journal Article] SynArfGEF is a guanine nucleotide exchage factor for Arf6 and localizes preferentially at post-synaptic specialization of inhibitory synapases (2011)
  • Author(s): Fukaya M, Kamata A, Hara Y, Tamaki H, Katsumata O, Ito N, Takeda S, Hata Y, Suzuki T, Watanabe M, Harvey RJ, Sakagami H
  • Journal Title: J. Neurochem Volume: 116 Pages: 1122-1137
  • DOI: 10.1111/j.1471-4159.2010.07167.x.
  • Peer Reviewed
• [Journal Article] Differential expression of SNAP-25 family proteins in the mouse brain (2011)
  • Author(s): Yamamori S, Itakura M, Sugaya D, Katsumata O, Sakagami H, Takahashi M
  • Journal Title: J. Comp. Neurol Volume: 519 Pages: 916-932
  • DOI: 10.1002/cne.22558
• [Journal Article] Locomotor-related activity of GABAergic interneurons localized in the ventrolateral region in the isolated spinal cord of neonatal mice (2011)
  • Author(s): Nishimaru H, Sakagami H, Kakizaki M, Yanagawa Y
  • Journal Title: J Neurophysiol Volume: 106(4) Pages: 1782-1792
  • DOI: 10.1152/jn.00385.2011
  • Peer Reviewed
• [Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons (2010)
  • Author(s): Sanda M, Ohara N, Kamata A, Hara Y, Tamaki H, Sukegawa J, Yanagisawa T, Fukunaga K, Kondo H, Sakagami H
  • Journal Title: Neurosci. Res Volume: 67(2) Pages: 126-136
  • DOI: 10.1016/j.neures.2010.02.008
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice (2010)
  • Author(s): Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H, Sakagami H, Miyakawa T
  • Journal Title: PLoS ONE Volume: e9460
  • DOI: 10.1371/journal.pone.0009460
  • Peer Reviewed
• [Journal Article] USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly (2010)
  • Author(s): Théard D, Labarrade F, Partisani M, Milanini J, Sakagami H, Fon EA, Wood SA, Franco M, Luton F
  • Journal Title: EMBO J Volume: 29 Pages: 1499-1509
  • DOI: 10.1038/emboj.2010.46
  • Peer Reviewed
• [Journal Article] Involvement of the serum response factor coactivator megakaryoblastic leukemia (MKL) in the activin-regulated dendritic complexity of rat cortical neurons (2010)
  • Author(s): Ishikawa M, Nishijima N, Shiota J, Sakagami H, Tsuchida K, Mizukoshi M, Fukuchi M, Tsuda M, Tabuchi A
  • Journal Title: J Biol Chem Volume: 285 Pages: 32734-32743
  • DOI: 10.1074/jbc.M110.118745
  • Peer Reviewed
• [Journal Article] Identification and characterization of PRG-1 as a neuronal calmodulin-binding protein (2010)
  • Author(s): Tokumitsu H, Hatano N, Tsuchiya M, Yurimoto S, Fujimoto T, Ohara N, Kobayashi R, Sakagami H
  • Journal Title: Biochem J Volume: 43 Pages: 81-91
  • DOI: 10.1042/BJ20100637
  • Peer Reviewed
• [Presentation] 脳層形成における低分子量GTP 結合タンパク質Arf6の機能的役割 (2014)
  • Author(s): 原芳伸、深谷昌弘、阪上洋行
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医大
  • Year and Date: 2014-03-29
• [Presentation] 海馬錐体細胞の棘突起内部における低分子量Gタンパク質Arf6 のペリシナプス性局在 (2014)
  • Author(s): 深谷昌弘、阪上洋行
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医大
  • Year and Date: 2014-03-28
• [Presentation] シナプス局在からみたArf6グアニンヌクレオチド交換因子の分子多様性の機能的意義 (2013)
  • Author(s): 阪上洋行
  • Organizer: 第86回日本生化学大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-09-13
• [Presentation] スパインにおけるArf6 活性化制御因子EFA6Aとsorting nexin-1との相互作用 (2013)
  • Author(s): 阪上洋行、福島大輔、深谷昌弘
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] Expression and functional roles of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) γ in the developing cerebral cortex (2012)
  • Author(s): 原芳伸、阪上洋行
  • Organizer: 欧州神経科学会
  • Place of Presentation: バルセロナ
  • Year and Date: 2012-07-15
• [Presentation] DISTINCT LOCALIZATION OF THE BRAG/IQSEC FAMILY OF GUANINE NUCLEOTIDE EXCHANGE FACTORS FOR ARF6 IN THE MOUSE RETINA (2012)
  • Author(s): 阪上洋行、原芳伸、深谷昌弘
  • Organizer: 欧州神経科学会議
  • Place of Presentation: バルセロナ
  • Year and Date: 2012-07-15