Common and distinct mechanisms for ARF6-mediated neuronal migration and cancer invasion

• Project/Area Number: 23659101
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Kitasato University
• Principal Investigator: SAKAGAMI Hiroyuki 北里大学, 医学部, 教授 (90261528)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経細胞 / がん細胞 / アクチン骨格 / 小胞輸送 / 運動性 / 低分子量 GTP 結合タンパク質 / 細胞骨格 / 低分子量GTP結合蛋白質 / 大脳皮質 / 層構造 / 子宮内電気穿孔法 / 低分子量G蛋白質 / 癌 / 細胞運動 / アクチン細胞骨格 / 接着分子 / 膜脂質

Research Abstract

ADP ribosylation factor is a small GTPase that regulate membrane traffic and actin remodeling through the activation of lipid modifying enzymes and recruitment of various interacting proteins such as FIP3/4 and JIP3/4. Recent evidence indicates the functional importance of ARF6 pathways in cell motility such as cancer invasion and metastasis. The aim of this study is to test the possibility whether the ARF6 pathway may be involved in neuronal migration during cortical layer formation. We found that type I phosphatidylinositol 4-phosphate 5-kinase r (PIP5KIr), a phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-synthesizing enzyme that functions as a downstream effector of Arf6, is required for neuronal migration possibly through recruitment of adhesion components to the plasma membrane.

Research Products

• [Journal Article] Type I phosphatidylinositol 4-phosphate 5-kinase r 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
  • 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: S0014- 5793(13) Pages: 298-6
  • NAID: 120005293580
  • 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
  • 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
  • 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 Issue: 4 Pages: 860-876
  • DOI: 10.1002/cne.23206
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Thromboxane A(2) receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment (2012)
  • Author(s): Minamino T, Ito Y, Ohkubo H, Hosono K, Suzuki T, Sato T, Ae T, Shibuya A, Sakagami H, Narumiya S, Koizumi W, Majima M
  • Journal Title: Toxicol Appl Pharmacol Volume: 259 Pages: 104-114
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of HOPX promotes cancer progression in colorectal cancer (2012)
  • Author(s): Katoh H, Yamashita K, Waraya M, Margalit O, Ooki A, Tamaki H, Sakagami H, Kokubo K, Sidransky D, Watanabe M
  • Journal Title: Neoplasia Volume: 14 Pages: 559-571
  • 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 Issue: 19 Pages: 3064-3070
  • DOI: 10.1016/j.febslet.2012.07.051
  • 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) Issue: 28 Pages: 23306-23317
  • DOI: 10.1074/jbc.m112.344762
  • 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 Issue: 48 Pages: 17186-17196
  • DOI: 10.1523/jneurosci.2220-12.2012
  • Peer Reviewed
• [Journal Article] Thromboxane A(2) receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment (2012)
  • Author(s): Minamino T, Ito Y, Ohkubo H, Hosono K, Suzuki T, Sato T, Ae T, Shibuya A, Sakagami H, Narumiya S, Koizumi W, Majima M
  • Journal Title: Toxicol Appl Pharmacol Volume: 259(1) Issue: 1 Pages: 104-14
  • DOI: 10.1016/j.taap.2011.12.013
  • Peer Reviewed
• [Journal Article] Epigenetic Silencing of HOPX Promotes Cancer Progression in Colorectal Cancer (2012)
  • Author(s): Katoh Hiroshi
  • Journal Title: NEOPLASIA Volume: 14 Issue: 7 Pages: 559-559
  • DOI: 10.1593/neo.12330
  • 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
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor receptor-1 signaling promotes liver repair through restoration of liver microvasculature after acetaminophen hepatotoxicity (2011)
  • Author(s): Kato T, Ito Y, Hosono K, Suzuki T, Tamaki H, Minamino T, Kato S, Sakagami H, Shibuya M, Majima M
  • Journal Title: Toxicol Sci Volume: 120 Pages: 218-229
  • Peer Reviewed
• [Journal Article] Roles of prostaglandin E2-EP3/EP4 receptor signaling in the enhancement of lymphangiogenesis during fibroblast growth factor-2-induced granulation formation (2011)
  • Author(s): Hosono K, Suzuki T, Tamaki H, Sakagami H, Hayashi I, Narumiya S, Alitalo K,Majima M
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31 Pages: 1049-1058
  • 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
  • Peer Reviewed
• [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 Pages: 1782-1792
  • Peer Reviewed
• [Journal Article] Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice (2011)
  • Author(s): Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S, DeClerck YA, Okamoto H, Majima M
  • Journal Title: Life Sci Volume: 88 Pages: 693-700
  • Peer Reviewed
• [Journal Article] Less invasive and less technically demanding decompressive procedure for lumbar spinal stenosis - appropriate for general orthopaedic surgeons? (2011)
  • Author(s): Takaso M, Nakazawa T, Imura T, Fukushima K, Ueno M, Saito W, Shintani R, Sakagami H, Takahashi K, Yamazaki M, Ohtori S, Kotani T
  • Journal Title: International Orthopaedics Volume: 35 Pages: 67-73
  • Peer Reviewed
• [Journal Article] SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapses (2011)
  • Author(s): Fukaya, M.; Kamata, A.; Hara, Y., et al
  • Journal Title: Journal of Neurochemistry Volume: 116(6) Issue: 6 Pages: 1122-1137
  • DOI: 10.1111/j.1471-4159.2010.07167.x
  • Peer Reviewed
• [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) Issue: 4 Pages: 1782-1792
  • DOI: 10.1152/jn.00385.2011
  • 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 Issue: 5 Pages: 916-932
  • DOI: 10.1002/cne.22558
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor receptor-1 signalingpromotes liver repair through restoration of liver microvasculature afteracetaminophen hepatotoxicity (2011)
  • Author(s): Kato T, Ito Y, Hosono K, Suzuki T, Tamaki H, Minamino T, Kato S, Sakagami H, Shibuya M, Majima M
  • Journal Title: Toxicol Sci Volume: 120(1) Issue: 1 Pages: 218-29
  • DOI: 10.1093/toxsci/kfq366
  • Peer Reviewed
• [Journal Article] Roles of prostaglandin E2-EP3/EP4 receptor signaling in the enhancement of lymphangiogenesis during fibroblast growth factor-2-induced granulation formation (2011)
  • Author(s): Hosono K, Suzuki T, Tamaki H, Sakagami H, Hayashi I, Narumiya S, Alitalo K, Majima M
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31(5) Issue: 5 Pages: 1049-58
  • DOI: 10.1161/atvbaha.110.222356
  • Peer Reviewed
• [Journal Article] Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice (2011)
  • Author(s): Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S, DeClerck YA, Okamoto H, Majima M
  • Journal Title: Life Sci Volume: 88(15-16) Issue: 15-16 Pages: 693-700
  • DOI: 10.1016/j.lfs.2011.02.008
  • Peer Reviewed
• [Presentation] xpression and functional roles of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) r in the developing cerebral cortex (2013)
  • Author(s): 原芳伸、深谷昌弘、玉木英明、阪上洋行
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] Splice variantdependent subcellular localization of the Arf6 activator BRAG2 in the adult mouse brain (2013)
  • Author(s): 深谷昌弘、阪上洋行
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] Arf6 の 下 流 効 果 分 子 Rab11-FIP3/Arfophilin-1 の神経細胞の樹状突起における役割 (2013)
  • Author(s): 矢崎佑紀、原芳伸、深谷昌弘、阪上洋行
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] Expression and functional roles of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) γ in the developing cerebral cortex. (2013)
  • Author(s): 原 芳伸
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川
• [Presentation] Splice variant-dependent subcellular localization of the Arf6 activator BRAG2 in the adult mouse brain (2013)
  • Author(s): 深谷 昌弘
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川
• [Presentation] Arf6の下流効果分子Rab11-FIP3/Arfophilin-1の神経細胞の樹状突起における役割 (2013)
  • Author(s): 矢崎 佑紀
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川
• [Presentation] 成熟マウス脳における Arf6 活性化制御因子EFA6A の細胞内局在解析 (2012)
  • Author(s): 福島大輔、深谷昌弘、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2012-03-28
• [Presentation] 成体マウス脳におけるARF6活性化因子BRAG2/IQSEC1 の細胞内局在解析 (2012)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2012-03-28
• [Presentation] マウス小脳プルキンエ細胞の生後発生過程におけるゴルジ装置の動態 (2012)
  • Author(s): 玉木英明、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2012-03-27
• [Presentation] 大脳皮質層形成におけるホスファチジルイノシトール4-リン酸5キナーゼの機能解析 (2012)
  • Author(s): 原芳伸、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2012-03-26
• [Presentation] ARF6 活性制御因子 BRAG2/IQSEC1 のスプライスバリアント依存的なシナプス局在 (2012)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第35回日本神経科学会
  • Place of Presentation: 名古屋
• [Presentation] 成熟マウス脳における EFA6A とおよびその結合分子 SNX1 の細胞内局在解析 (2012)
  • Author(s): 福島大輔、深谷昌弘、阪上洋行
  • Organizer: 第35回日本神経科学会
  • Place of Presentation: 名古屋
• [Presentation] Expression and functional roles of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) r in the developing cerebral cortex (2012)
  • Author(s): 原芳伸、阪上洋行
  • Organizer: 第8回欧州神経科学会 (FENS)
  • Place of Presentation: スペイン
• [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: 第8回欧州神経科学会 (FENS)
  • Place of Presentation: スペイン
• [Presentation] Expression and functional roles of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) γ in the developing cerebral cortex. (2012)
  • Author(s): Hara Yoshinobu
  • Organizer: 8th Federation of European Neuroscience Societies (FENS) Meeting
  • Place of Presentation: バルセロナ スペイン
• [Presentation] DISTINCT LOCALIZATION OF THE BRAG/IQSEC FAMILY OF GUANINE NUCLEOTIDE EXCHANGE FACTORS FOR ARF6 IN THE MOUSE RETINA (2012)
  • Author(s): Sakagami Hiroyuki
  • Organizer: 8th Federation of European Neuroscience Societies (FENS) Meeting
  • Place of Presentation: バルセロナ スペイン
• [Presentation] ARF6活性制御因子BRAG2/IQSEC1のスプライスバリアント依存的なシナプス局在 (2012)
  • Author(s): 深谷 昌弘
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] 成熟マウス脳におけるEFA6Aとおよびその結合分子SNX1の細胞内局在解析 (2012)
  • Author(s): 福島大輔
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] マウス小脳プルキンエ細胞の生後発生過程におけるゴルジ装置の動態 (2012)
  • Author(s): 玉木英明、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学（山梨県）
• [Presentation] 大脳皮質層形成におけるホスファチジルイノシトール４－リン酸５キナーゼの機能 (2012)
  • Author(s): 原芳伸、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学（山梨県）
• [Presentation] 成熟マウス脳におけるArf6活性化制御因子EFA6Aの細胞内局在解析 (2012)
  • Author(s): 福島大輔、深谷昌弘、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学（山梨県）
• [Presentation] 成体マウス脳におけるARF6活性化因子BRAG2/IQSEC1の細胞内局在解析 (2012)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学（山梨県）
• [Presentation] 大脳皮質形成におけるホスファチジルイノシトール4-リン酸5キナーゼの機能解析 (2011)
  • Author(s): 原芳伸、西村伸彦、深谷昌弘、玉木英明、阪上洋行
  • Organizer: 第99回日本解剖学関東支部学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-15
• [Presentation] 中枢神経系における ARF6 活性化制御因子 EFA6Aの細胞内局在解析 (2011)
  • Author(s): 福島大輔、深谷昌弘、阪上洋行
  • Organizer: 第99回日本解剖学関東支部学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-15
• [Presentation] 成熟期マウス脳における BRAG2/GEP100 の細胞内局在解析 (2011)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-17
• [Presentation] 大脳皮質層形成における PIP5Kgamma の発現機能解析 (2011)
  • Author(s): 原芳伸、西村伸彦、阪上洋行
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] 大脳皮質層形成におけるPIP5Kgammaの発現機能解析 (2011)
  • Author(s): 原芳伸、西村伸彦、阪上洋行
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] マウス新生児脊髄腹側において同側に投射する抑制性ニューロンの機構的・形態学的解析 (2011)
  • Author(s): 西丸広史、阪上洋行、柿崎美代、柳川右千夫
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 成熟期マウス脳におけるBRAG2/GEP100の細胞内局在解析 (2011)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] アクチン結合性転写活性因子MKLが関与するアクチビン誘導性のラット大脳皮質ニューロン樹状突起形態制御における新規シグナル伝達経路の解析 (2011)
  • Author(s): 石川充、西嶋直紀、阪上洋行、土田邦博、水越美帆、塩田惇、福地守、津田正明、田渕明子
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Remarks] 北里大学医学部解剖学教室ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/~sakagami/
• [Remarks] 北里大学医学部解剖学（阪上）単位ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/~sakagami/
• [Remarks]
  • URL: http://www.med.kitasato-u.ac.jp/~sakagami/