Regulation of endosome formation and recycling by Cdk5/p35 in neurons

• Project/Area Number: 20370047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: HISANAGA Shin-ichi Tokyo Metropolitan University, 大学院・理工学研究科, 教授 (20181092)
• Co-Investigator(Kenkyū-buntansha): ASADA Akiko 首都大学東京, 大学院・理工学研究科, 助教 (00336512)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: CIN85 / AATYK / Cdk5 / エンドソーム / エンドサイトーシス / リサイクリング / AAYK1 / 神経細胞 / リン酸化 / AATYK1

Research Abstract

CIN85 is an adapter protein involved in endocytosis and AATYK1 is a Ser/Thr kinase expressed highly in neurons. We found recently that both were phosphorylated by Cdk5. We studied roles of their Cdk5 phosphorylation in neurons. AATYK1 was shown to regulate recycling endosomal trafficking and the activity was suppressed by phosphorylation with Cdk5. AATYK1 activity is involved in axonal elongation. The function of CIN85 is not known. We generated a specific antibody to investigate endogenous CIN85 localization in neurons. CIN85 was present as small particles in neuronal soma and process, which were thought to be very early endocytic structures.

Research Products

• [Journal Article] Regulation and role of Cdk5 kinase activity in neuronal survival and death. (2010)
  • Author(s): Hisanaga, S., Endo, E.
  • Journal Title: J. Neurochem. 115 Pages: 1309-1321
  • Peer Reviewed
• [Journal Article] Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39. (2010)
  • Author(s): Minegishi, S., Asada, A., Miyauchi, S., Fuchigami, T., Saito, T., Hisanaga, S.
  • Journal Title: Biochemistry 49 Pages: 5482-5493
  • Peer Reviewed
• [Journal Article] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway. (2010)
  • Author(s): Takano, T., Tsutsumi, K., Saito, T., Asada, A., Tomomura, M., Fukuda, M., Hisanaga S.
  • Journal Title: Genes Cells 15 Pages: 783-797
  • Peer Reviewed
• [Journal Article] Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation. (2010)
  • Author(s): Tsutsumi, K., Takano, T., Endo, R., Fukuda, M., Ohshima, T., Tomomura, M., Hisanaga S.
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] Quantitative Measurement of In Vivo Phosphorylation States of Cdk5 Activator p35 by Phos-tag SDS-PAGE. (2010)
  • Author(s): Hosokawa T., Saito, T., Asada, A., Fukunaga, K., Hisanaga S.
  • Journal Title: Mol.Cell.Proteomics. 9 Pages: 1133-1143
  • Peer Reviewed
• [Journal Article] Neuronal expression of two isoforms of mouse Septin 5. (2010)
  • Author(s): Asada, A., Takahashi, J., Taniguchi, M., Yamamoto, H., Kimura, T., Saito, T., Hisanaga S.
  • Journal Title: J.Neurosci.Res. 88 Pages: 1309-1316
  • Peer Reviewed
• [Journal Article] Cdk5-シナプスにおけるネガティブレギュレーター (2010)
  • Author(s): 細川智永、久永真市
  • Journal Title: 生体の科学特集号「シナプスをめぐるシグナリング」 61 Pages: 470-471
• [Journal Article] Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39. (2010)
  • Author(s): Minegishi, S., et al.
  • Journal Title: Biochemistry Volume: 49 Pages: 5482-5493
  • Peer Reviewed
• [Journal Article] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway. (2010)
  • Author(s): Takano, T., et al.
  • Journal Title: Genes Cells Volume: 15 Pages: 783-797
  • Peer Reviewed
• [Journal Article] Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation. (2010)
  • Author(s): Tsutsumi, K., et al.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Commitment of MPP+-induced neuronal cell death by proteasome-mediated degradation of p35 Cdk5 activator. (2009)
  • Author(s): Endo, R., Saito, T.,Asada, A., Kawahara, H., Ohshima, T., Hisanaga S.
  • Journal Title: J.Biol.Chem. 284 Pages: 26029-26039
  • Peer Reviewed
• [Journal Article] Novel axonal distribution of neurofilament-H phosphorylated at the GSK3β-phosphorylation site in its E-segment. (2009)
  • Author(s): Sasaki, T., Ishiguro, K., Hisanaga S.
  • Journal Title: J.Neurosci.Res. 87 Pages: 3088-3097
  • Peer Reviewed
• [Journal Article] Effect of pin1 or microtubule binding on dephosphorylation of FTDP-17 mutant tau. (2009)
  • Author(s): Yotsumoto, K., Saito, T., Asada, A., Oikawa, T., Kimura, T., Uchida, C., Ishiguro, K., Uchida, T., Hasegawa, M., Hisanaga S.
  • Journal Title: J.Biol.Chem. 284 Pages: 16840-16847
  • Peer Reviewed
• [Journal Article] 多様な神経機能を制御するキナーゼCdk5 (2009)
  • Author(s): 久永真市
  • Journal Title: 蛋白質核酸酵素 54
• [Journal Article] Effect of pinl or microtubule binding on dephosphorylation of FTDP-17 mutant tau. (2009)
  • Author(s): Yotsumoto, et al.
  • Journal Title: J.Biol. Chem. 284 Pages: 16840-16847
  • Peer Reviewed
• [Journal Article] Effect of pins or microtubule binding on dephosphorylation of FTDP-17 mutant tau. (2009)
  • Author(s): Sasaki, et al.
  • Journal Title: J.Neurosci. Res. 87 Pages: 3088-3097
  • Peer Reviewed
• [Journal Article] Commitment of MPP+-induced neuronal cell death by proteasome-mediated degradation of p35 Cdk5 activator. (2009)
  • Author(s): Endo, et al.
  • Journal Title: J.Biol. Chem. 284 Pages: 26029-26039
  • Peer Reviewed
• [Journal Article] Suppression of mutant huntingtin aggregate formation by Cdk5/p35 through the effect on microtubule stability. (2008)
  • Author(s): Kaminosono, S., Saito, T., Oyama, F., Ohshima, T., Asada, A., Nagai, Y., Nukina, N., Hisanaga S.
  • Journal Title: J.Neurosci. 28 Pages: 8747-8755
  • Peer Reviewed
• [Journal Article] Palmitoylation-dependent endosomal localization of AATYK1A and its interaction with Src. (2008)
  • Author(s): Tsutsumi, K., Tomomura, M., Furuichi, T., Hisanaga S.
  • Journal Title: Genes to Cells 13 Pages: 949-964
  • Peer Reviewed
• [Journal Article] Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cycline-dependent kinase 5 (Cdk5) complexes. (2008)
  • Author(s): Asada, A., Yamamoto, N., Gohda, M., Saito, T., Hayashi, N., Hisanaga S.
  • Journal Title: J.Neurochem. 106 Pages: 1325-1336
  • Peer Reviewed
• [Journal Article] Suppression of mutant huntingtin aggregate formation by Cdk5/p35 through the effect on microtubule stability. (2008)
  • Author(s): Kaminosono, et al.
  • Journal Title: J. Neurosci. 28 Pages: 8747-8755
  • Peer Reviewed
• [Journal Article] Palmitoylation-dependent endosomal localization of AATYK1A and its interaction with Src. (2008)
  • Author(s): Tsutsumi, et al.
  • Journal Title: Gene to Cell 13 Pages: 949-964
  • Peer Reviewed
• [Journal Article] Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cycline-dependent kinase 5 (Cdk5)complexes. (2008)
  • Author(s): Asada, et al.
  • Journal Title: J. Neurochem. 106 Pages: 1325-1336
  • Peer Reviewed
• [Journal Article] Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25.
  • Author(s): Sato, K., Minegishi, S., Takano, J., Plattner, F., Saito, T., Asada, A., Kawahara, H., Iwata, N., Saido, T.C., Hisanaga S.
  • Journal Title: J. Neurochem. In press
  • Peer Reviewed
• [Presentation] Normal and abnormal phosphorylation of Tau by Cyclin-dependent kinase 5 (2010)
  • Author(s): Hisanaga, S.
  • Organizer: Aging, Tau Protein and Dementias.
  • Place of Presentation: 東京
  • Year and Date: 2010-10-20
• [Presentation] Cdk5 and neuron cell death. (2010)
  • Author(s): 久永眞市
  • Organizer: Pep Con-2010
  • Place of Presentation: 北京
• [Presentation] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway. (2010)
  • Author(s): 高野哲也
  • Organizer: 第62回日本細胞生物学会
  • Place of Presentation: 大阪
• [Presentation] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway. (2010)
  • Author(s): 高野哲也
  • Organizer: 第53回日本神経化学会
  • Place of Presentation: 神戸
• [Presentation] Normal and abnormal phosphorylation of Tau by Cyclin-dependent kinase 5. (2010)
  • Author(s): 久永眞市
  • Organizer: Aging, Tau Protein and Dementias.
  • Place of Presentation: 東京
• [Presentation] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway-A role of AATYK1 in axon outgrowth- (2010)
  • Author(s): 高野哲也
  • Organizer: アメリカ神経科学会
  • Place of Presentation: サンディエゴ
• [Presentation] AATYK1A phosphorylation by Cdk5 regulates the neurite outgrowth via recycling endosome pathway. (2010)
  • Author(s): 高野哲也
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] p35/Cdk5とp39/Cdk5の細胞内局在に及ぼすCdk5キナーゼ活性の影響 (2010)
  • Author(s): 浅田明子
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Neuronal development and neurodegeneration on Cdk5 and related signaling (2009)
  • Author(s): Hisanaga, S
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-17
• [Presentation] AATYKのエンドソーム局在と神経突起伸展作用に対するCdk5の影響 (2009)
  • Author(s): 堤弘次
  • Organizer: 第61回日本細胞生物学会
  • Place of Presentation: 名古屋
• [Presentation] Reconsideration of the activation mechanism of Cdk5 by p35 and p39. (2009)
  • Author(s): 久永眞市
  • Organizer: 2^<nd> International Symposium on Cdk5.
  • Place of Presentation: 東京
• [Presentation] Effect of PIN1 and microtubules binding on dephosphorylation of FTDP-17 mutant Tau. (2009)
  • Author(s): 久永眞市
  • Organizer: 2009 International Conference on Alzheimer's Disease.
  • Place of Presentation: ウィーン
• [Presentation] フォスタグSDS-PAGEを用いたタンパク質リン酸化の解析-Cdk5活性化サブユニットp35の場合- (2009)
  • Author(s): 久永眞市
  • Organizer: 第7回ヒトプロテオーム学会
  • Place of Presentation: 東京
• [Presentation] サイクリン依存性キナーゼ5(Cdk5)の異常活性化と神経変性疾患 (2009)
  • Author(s): 久永眞市
  • Organizer: 「筋萎縮性側索硬化症の病態に基づく画期的治療法の開発」班のワークショップ
  • Place of Presentation: 東京
• [Presentation] Neuronal development and neurodegeneration on Cdk5 and related signaling. (2009)
  • Author(s): 久永眞市
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] タンパク質リン酸化研究へのフォスタグSDS-PAGEの応用 (2009)
  • Author(s): 久永眞市
  • Organizer: 第4回日本プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 熊本
• [Presentation] AATYK1Aのリサイクリングエンドソーム輸送活性はCdk5-p35によって制御される (2009)
  • Author(s): 高野哲也
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Pro-survival and pro-apoptotic activity of neuron-specific protein kinase Cdk5. (2009)
  • Author(s): 久永眞市
  • Organizer: 27th Annual conference of Indian Academy of Neuroscience
  • Place of Presentation: インド
• [Presentation] Cdk5 and Neuron Cell Death. (2009)
  • Author(s): 久永眞市
  • Organizer: 3^<rd> Annual Protein and Peptide Conference (PepCon-2010)
  • Place of Presentation: 北京
• [Presentation] Cdk5 and Microtubules in Neurodegenerative Diseases. (2009)
  • Author(s): 久永眞市
  • Organizer: The International Symposium on "Cell Cycle and Cell Architecture".
  • Place of Presentation: Nagoya
• [Presentation] サイクリン依存性キナーゼ5の活性制御と神経変性疾患 (2009)
  • Author(s): 久永眞市
  • Organizer: 第31回日本分子生物学会シンポジウム
  • Place of Presentation: 神戸
• [Presentation] サイクリン依存性キナーゼ5の活性制御と神経変性疾患。 (2008)
  • Author(s): 久永眞市, 淺田明子, 斎藤太郎
  • Organizer: 第31回日本分子生物学会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Filament assembly abnormality of neurofilament-L with Charcot-Marie-Tooth disease mutation. (2008)
  • Author(s): 久永眞市
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] 前頭側頭葉認知症(FTDP-17)変異型タウの脱リン酸化 (2008)
  • Author(s): 浅田明子
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Regulation of endosomal localization of AATYK1A and its interaction with Src by palmitoylation. (2008)
  • Author(s): 堤弘次
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
• [Presentation] p35/Cdk5とp39/Cdk5の細胞内局在に及ぼすCdk5キナーゼ活性の影響 (2008)
  • Author(s): 浅田明子
  • Organizer: 第31回日本分子生物学会大会
  • Place of Presentation: 神戸
• [Presentation] CIN85の神経細胞における発現及びDab1との相互作用について (2008)
  • Author(s): 渕上孝裕
  • Organizer: 第31回分子生物学会年会
  • Place of Presentation: 神戸
• [Book] 分子生物学(細胞機能)(田沼靖一編)第3版の第12章 (2011)
  • Author(s): 久永眞市
  • Publisher: 丸善
• [Book] 細胞周期フロンティア(神経細胞におけるCdk5-p35の活用戦略)(佐方功幸・稲垣昌樹・岸本健雄編集) (2010)
  • Author(s): 久永眞市, 遠藤良
  • Publisher: 共立出版
• [Book] Neurofilaments in aged amimals.Cytoskeleton of the Nervous System. (2010)
  • Author(s): Hisanaga, S., et al.
  • Total Pages: 11
  • Publisher: Springer
• [Book] The Kinase Activity of Cdk5 and Its Regulation. In Cdk5 book(eds. Ip, N. and Tsai, L-H.) (2008)
  • Author(s): Hisanaga S., Ishiguro, K.
  • Publisher: Splinger, NY
• [Book] The Kinase Activity of Cdk5 and Its Regulation. In Cdk5 book (2008)
  • Author(s): Hisanaga, S., Ishiguro, K.
  • Total Pages: 13
  • Publisher: Splinger, NY
• [Book] Neurofilaments in aged amimals. Cytoskeleton of the Nervous System. Advances in Neurobiology 3.(Eds. By R. Nixon and A Yuan)
  • Author(s): Hisanaga S., Sasaki, T., Uchida, A.
  • Publisher: Springer
• [Remarks]
  • URL: http://www.sci.metro-u.ac.jp/mnc/
• [Remarks]
  • URL: http://www.sci.metro-u.ac.jp/mnc/
• [Remarks]
  • URL: http://www.sci.metro-u.ac.jp/mnc/