Mechanism of kinesin-1 activation by cargo receptor

• Project/Area Number: 22659011
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: SUZUKI Toshiharu 北海道大学, 大学院・薬学研究院, 教授 (80179233)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 細胞生物学 / キネシン / 膜小胞輸送 / カーゴ / Alcadein / 微小管 / 分子モーター / アルカデイン

Research Abstract

Kinesin-1 anterogradely transports vesicles containing cargo proteins when a prptein-protein interaction activates it from an inhibited state. The C-terminal cytoplasmic region of Alcadein interacts with the kinesin light-chain KLC tetratricopeptide repeat(TPR) region, activating kinesin-1 association with vesicles and anterograde transport. Only 10 amino acids WD motif was enough to activate kinesin-1 motor. This mechanism contributes to explain how kinesin-1 can organize the transport of a wide variety of cargo molecules.

Research Products

• [Journal Article] A small peptide sequence is sufficient for initiating kinesin-1 activation through part of TPR region of KLC1 (2012)
  • Author(s): Kawano, T., Araseki, M., Araki, Y., Kinjo, M., Yamamoto, T. and Suzuki, T.
  • Journal Title: Traffic Volume: 13 Pages: 834-848
  • Peer Reviewed
• [Journal Article] FE65 as a link between VLDLR and APP to regulate their trafficking and processing. (2012)
  • Author(s): Dumanis, S., Chamberlain, K. A., Sohn, Y. J., Lee, Y. J., Guenette, S. Y., Suzuki, T., Mathews, P. W., Pak, D. T. S., Rebexk, G. W., Suh, Y-h., Park, H-S., Hoe, H-S.
  • Journal Title: Mol. Neurodegen Volume: 7 Issue: 1 Pages: 9-9
  • DOI: 10.1186/1750-1326-7-9
  • Peer Reviewed
• [Journal Article] Improvement of cognitive function in Alzheimer's disease model mice by genetic and pharmacological inhibition of the EP(4) receptor (2012)
  • Author(s): Hoshino T, Namba T, Takehara M, Murao N, Matsushima T, Sugimoto Y, Narumiya S, Suzuki T, Mizushima T
  • Journal Title: J.Neurochem. Volume: 120 Issue: 5 Pages: 795-805
  • DOI: 10.1111/j.1471-4159.2011.07567.x
  • Peer Reviewed
• [Journal Article] Effects of heparin and enoxaparin on APP processing and Ab production in primary cortical neurons from Tg2576 mouse (2011)
  • Author(s): Cui, H., Hung, A. C., Klaver, D. W., Suzuki, T., Freeman, C., Narkowicz, C., Jacobson, G. and Small, D. H.
  • Journal Title: PLoS One Volume: 6 Issue: 7 Pages: e23007-e23007
  • DOI: 10.1371/journal.pone.0023007
  • Peer Reviewed
• [Journal Article] Intracellular trafficking of the amyloid β-protein precursor (APP) regulated by novel function of X11-like (2011)
  • Author(s): Saito Y
  • Journal Title: PLoS One Volume: 6 Issue: 7 Pages: e22108-e22108
  • DOI: 10.1371/journal.pone.0022108
  • Peer Reviewed
• [Journal Article] Cystein-rich intestinal protein 2(CRIP2) acts as a repressor of NFkB-mediated pro-angiogenic cytokins transcription to suppress tumorigenesis and angiogenesis (2011)
  • Author(s): Cheung, K. L., Ko, JMY, Lung H-L., Chang K-W., Stanbridge, E. J., Zabarovsky, E. R., Tokino, T., Kashima, L., Suzuki, T., Kwong, D L-w., Chua, D., Tsao, S. W., Lung, M. L.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Pages: 8390-8395
  • Peer Reviewed
• [Journal Article] Alternative g-secretase processing of g-secretase substrates in common forms of mild cognitive impairment and Alzheimer disease : Evidence for g-secretase dysfunction (2011)
  • Author(s): Hata, S., Fujishige, S., Araki, Y., Taniguchi, M., Urakami, K., Peskind E., Akatsu, H., Araseki, M., Yamamoto, K., Martins, N. R., Maeda, M., Nishimura, M., Levey, A., Chung, K. A., Montine, T., Leverenz, J., Fagan, A., Goate, A., Bateman, R., Holtzman, D. M., Yamamoto, T., Nakaya, T., Gandy, S. and Suzuki, T.
  • Journal Title: Ann. Neurol Volume: 69 Pages: 1026-1031
  • Peer Reviewed
• [Journal Article] Suppression of Alzheimer's disease-related phenotypes by expression of heat shock protein 70 in mice. (2011)
  • Author(s): Hoshino T, Murao N, Namba T, Takehara M, Adachi H, Katsuno M, Sobue G, Matsushima T, Suzuki T, Mizushima T.
  • Journal Title: J Neurosci. Volume: 31 Issue: 14 Pages: 5225-5234
  • DOI: 10.1523/jneurosci.5478-10.2011
  • Peer Reviewed
• [Journal Article] Alternative processing of γ-secretase substrates in common forms of mild cognitive impairment and Alzheimer's disease : evidence for γ-secretase dysfunction (2011)
  • Author(s): Hata S
  • Journal Title: Ann.Neurol. Volume: 69 Issue: 6 Pages: 1026-1031
  • DOI: 10.1002/ana.22343
  • Peer Reviewed
• [Journal Article] Cystein-rich intestinal protein 2 (CRIP2) acts as a repressor of NFkB-mediated pro-angiogenic cytokins transcription to suppress tumorigenesis and angiogenesis (2011)
  • Author(s): Cheung, K.L., 7名略, Suzuki, T., 4名略
  • Journal Title: Proceeding of National Academy of Science USA Volume: 108 Issue: 20 Pages: 8390-8395
  • DOI: 10.1073/pnas.1101747108
  • Peer Reviewed
• [Journal Article] Coordinated increase of y-secretase products in the plasma of some female Japanese sporadic Alzheimer's disease patients: quantitative analysis of p3-Alca with a new ELISA system (2011)
  • Author(s): Konno, et al.
  • Journal Title: Molecular Neurodegeneration Volume: 6 Issue: 1 Pages: 76-76
  • DOI: 10.1186/1750-1326-6-76
  • Peer Reviewed
• [Journal Article] Alternative processing of γ-secretase substrates in common forms of mild cognitive impairment and Alzheimer's disease : Evidence for γ-secretase dysfunction (2011)
  • Author(s): Hata S, Fujishige S,(20名略), Gandy S, Suzuki T.
  • Journal Title: Annals of Neurology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Role of the intramolecular regions of FE65 in its trans-accumulation and in p53 stabilization in the nuclear matrix of osmotically stressed cells (2010)
  • Author(s): Kawai, T., Nakaya, T., and Suzuki, T.
  • Journal Title: FEBS Lett Volume: 584 Pages: 765-769
  • Peer Reviewed
• [Journal Article] The cytoplasmic adaptor protein X11a and extracellular matrix protein Reelin regulate ApoE receptor 2 trafficking and cell movement (2010)
  • Author(s): Minami, S. S., Sung Y. M., Dumanis, S. B., Chi, S. H., Burns, M. P., Ann, E-J., Suzuki, T., Tuner, R. S., Park, H-S., Pak, D. T. S., Rebeck, G. W. and Hoe, H-S.
  • Journal Title: FASEB J. Volume: 24 Pages: 58-69
  • Peer Reviewed
• [Journal Article] Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain. (2010)
  • Author(s): Kondo M, Shiono M,(7名略), Saito, Y., Suzuki, T.
  • Journal Title: Molecular Neurodegeneration Volume: 5
  • NAID: 120005158908
  • Peer Reviewed
• [Journal Article] Role of the intramolecular regions of FE65 in its trans-accumulation and in p53 stabilization in the nuclear matrix of osmotically stressed cells (2010)
  • Author(s): Kawai T, Nakaya T, Suzuki T.
  • Journal Title: FEBS Letter Volume: 24 Pages: 58-69
  • Peer Reviewed
• [Presentation] APP代謝・輸送制御を担うX11Like(X11L)の機能ドメイン (2012)
  • Author(s): 方家、斎藤有紀、鈴木利治
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)
• [Presentation] Molecular mechanism of kinesin-1 activation by Alcadeinα (2011)
  • Author(s): Araseki, M., Kawano, T., Araki, Y., Kinjo, M., Yamamoto, T., Suzuki, T.
  • Organizer: 51th The American Society for Cell Biology annual meeting
  • Place of Presentation: Colorado Convention Center(USA)
• [Presentation] Intracellular Trafficking of the Amyloidβ-Protein Precursor Regulated by PDZ domains of X11-Like (2011)
  • Author(s): Saito, Y., Suzuki, T.
  • Organizer: 51th The American society for cell biology annual meeting
  • Place of Presentation: Colorado Convention Center(USA)
• [Presentation] JIP-KLC1結合によるAPP輸送の効率化 (2011)
  • Author(s): 千葉杏子、野澤啓輔、荒関雅彦、齋藤有紀、金城政孝、鈴木利治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] Quantification of plasma p3-Alca level with sELISA systems (2011)
  • Author(s): Fang, J., Konno, T., Horikoshi-Sakuraba, Y., Hata, S., Saito, Y., Maeda, M., Akatsu, H., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles(France)
• [Presentation] Alternative gamma-secretase processing in sporadic Alzheimer's disease suggested by p3-Alc peptide, metabolic product of Alcadein (2011)
  • Author(s): Hata, S., Urakami, K., Taniguchi, M., Akatsu, H., Gandy, S., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles(France)
• [Presentation] Intracellular trafficking and metabolism of APP regulated by novel function of X11L (2011)
  • Author(s): Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011 "Developing Topics"
  • Place of Presentation: Porte de Versailles(France)
• [Presentation] Molecular mechanism of JIP1b-mediated APP association to kinesin-1 in APP transport and metabolic regulation (2011)
  • Author(s): Chiba, K., Nozawa, K., Araseki, M., Kinjo, M., Taru, H., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles(France)
• [Presentation] Increased levels of soluble p3-Alcadeinα in plasma of patients with Alzheimer's disease (2011)
  • Author(s): Kamogawa, K., Kohara, K., 10名略., Suzuki, T.
  • Organizer: American Academy of Neurology 63rd AAN Annual meeting
  • Place of Presentation: Hawai'I Convention Center (USA)
• [Presentation] Malfunction of HCN chanels in X11/X11L doubly deficient mice (2011)
  • Author(s): Saito, Y., Inoue, T., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Molecular mechanism of JIP1b-mediated APP association to kinesin-1 in APP transport and metabolic regulation (2011)
  • Author(s): Chiba, K., 4名略., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Enhanced amyloidogenic processing of APP in Alcadein-deficient mice (2011)
  • Author(s): Gotoh, N., 4名略., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Quantification of plasma p3-Alcα level with sELISA systems (2011)
  • Author(s): Fang, J., 6名略., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Alternative gamma-secretase processing in sporadic Alzheimer's disease suggested by p3-Alc peptide, metabolic product of Alcadein (2011)
  • Author(s): Hata, S., 4名略., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] APP metabolism in brain of Alcadein alpha CTF transgenic mice (2011)
  • Author(s): Kimura, A., 3名略., Suzuki, T
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Alcadeine epsilon-cleavage followed by gamma-cleavage (2011)
  • Author(s): Piao, Y., Hata, S., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Intracellular trafficking and metabolism of APP regulated by novel function of X11L (2011)
  • Author(s): Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Altered processing of gamma-secretase substrates and clearance of peptide products (Abeta and p3-Alc) as a pathogenesis of sporadic Alzheimer's disease. in "Invited Symposium 2-The pathological mechanisms underlying Alzheimer's disease" (2011)
  • Author(s): Suzuki, T., Hata, S.
  • Organizer: Gerontology & Geriatrics 2011
  • Place of Presentation: Melbourne Convention and Exhibition Center (Australia)(招待講演)
• [Presentation] Intracellular Trafficking of the Amyloid β-Protein Precursor Regulated by PDZ domains of X11-Like (2011)
  • Author(s): Saito, Y, Suzuki, T.
  • Organizer: 51th The American society for cell biology annual meeting
  • Place of Presentation: Colorado Convention Center (USA)
• [Presentation] Molecular mechanism of kinesin-1 activation by Alcadeinα (2011)
  • Author(s): Araseki, M., 4名略., Suzuki, T.
  • Organizer: 51th The American society for cell biology annual meeting
  • Place of Presentation: Colorado Convention Center (USA)
• [Presentation] アルツハイマー病におけるγセクレターゼの機能変化を反映するAlcadein膜内の切断機構の解析 (2011)
  • Author(s): 朴懿、羽田沙緒里、鈴木利治
  • Organizer: 第16回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪)
• [Presentation] アルツハイマー病の新たな生化学的マーカー、p3-Alcの早期診断マーカーとしての可能性の検証 (2011)
  • Author(s): 羽田沙緒里、浦上克哉、谷口美也子、池内健、鈴木利治
  • Organizer: 第1回日本認知症予防学会学術集会
  • Place of Presentation: 米子コンベンションセンター(鳥取)
• [Presentation] Alcadeinのγセクレターゼによる膜内切断機構の解明 (2011)
  • Author(s): Piao Yi(朴懿)、羽田沙緒里、鈴木利治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] リン酸化によるAPPの膜マイクロドメインへの移行制御機構の解析 (2011)
  • Author(s): 松島隆英、鈴木利治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] アポリポタンパク質EによるAlcadein代謝への影響 (2011)
  • Author(s): 木村彩乃、羽田沙緒里、鈴木利治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] JIP-KLCl結合によるAPP輸送の効率化 (2011)
  • Author(s): 千葉杏子、野澤啓輔、荒関雅彦、齋藤有紀、金城政孝、鈴木利治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] Role of Jip1b in the fast axonal transport of APP by kinesin-1 in neuron (2010)
  • Author(s): Araseki, M., Nozawa, K., Furukori, K., Davis, R. J., Taru, H., Kinjo, M., Suzuki, T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Pennsylvania Convention Center(USA)
• [Presentation] Intracellular dynamics of a kinesin-1 cargo Alcadein (2010)
  • Author(s): Gotoh, N., Maruta, C., Suzuki, T., Yamamoto, T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Pennsylvania Convention Center(USA)
• [Presentation] Alcadein as a kinesin-1 cargo receptor with motor regulation (2010)
  • Author(s): Suzuki, T., Matsushima, T., Kawano, T., Araki, Y., Kinjjo, M., Yamamoto, T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Pennsylvania Convention Center(USA)
• [Presentation] APP輸送において働く分子: JIP1bとKLCの結合機構の詳細 (2010)
  • Author(s): 千葉杏子、野澤啓輔、内藤志保、多留偉功、鈴木利治
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: ウインクあいち(愛知)
• [Presentation] γ-secretase dysfunction in sporadic Alzheimer's disease suggested by p3-Alc peptide, metabolic product of Alcadein. (2010)
  • Author(s): Hata, S., Urakami, K., Fagan, A., Peskind, E., Akatsu, H., Maeda, M., Levey, A., Chung, K. A., Montine, T., Leverenz, J., Goate, A., Bateman, R., Holzman, D. M., Gandy, S., and Suzuki, T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Hawai'I Convention Center(USA)
• [Presentation] Functional reagion of X11L in the regulation of APP metabolism and trafficking (2010)
  • Author(s): Shiono, M., Akiyama, M., Saito, Y. and Suzuki, T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Hawai'I Convention Center(USA)
• [Presentation] Expression and localization of Alcadein along with X11L and APP in mouse brain (2010)
  • Author(s): Piao, Y., Gotoh, N., Kondo, M., Saito, Y., Hata, S., Yamamoto, T. and Suzuki, T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Hawai 'I Convention Center(USA)
• [Presentation] Regulation of APPα-secretase activity involuved in protein palmitoylation by DHHC-12 (2010)
  • Author(s): Suzuki, T., and Mizumaru, C.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Hawai'I Convention Center(USA)
• [Presentation] Expression and localization of Alcadein along with X11L and APP in mouse brain. (2010)
  • Author(s): Piao Y, Gotoh N, Kondo M, Saito Y, Suzuki T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Neural activity and APP metabolism in the brain of X11/X11L doubly-deficient mice. (2010)
  • Author(s): Saito Y, Inoue T, Suzuki T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Regulation of APP α-secretase activity involved in protein palmitoylation by DHHC-12. (2010)
  • Author(s): Suzuki T., Mizumaru C.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Functional reagion of X11L in the regulation of APP metabolism and trafficking. (2010)
  • Author(s): Shiono, M., Akiyama, M., Saito, Y., Suzuki, T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] γ-secretase dysfunction in sporadic Alzheimer's disease suggested by p3-Alc peptide, metabolic product of Alcadein. (2010)
  • Author(s): Hata S.,(12名略), Gandy S., Suzuki, T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Increased p3-Alcα, a γ-secrelase reaction product of Alcadein, in plasma of sporadic Alzheimer's disease subjects. (2010)
  • Author(s): Konno T, Hata S,(7名略), Suzuki T.
  • Organizer: Alzheimer's Association ICAD2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Alcadein as a kinesin-1 cargo receptor with motor regulation. (2010)
  • Author(s): Suzuki, T.,(5名略)
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Intracellular dynamics of a kinesin-1 cargo Alcadein. (2010)
  • Author(s): Gotoh N., Maruta C., Suzuki T, Yamamoto T
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] p3-Alc peptides are generated by α and γ-sexretase cleavage of Alcadein and indicate Alzheimer's disease-related γ-secretase dysfunction. (2010)
  • Author(s): Hata, S., Suzuki, T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] A novel secretary pathway of amyloid precursor protein mediated by X11-like. (2010)
  • Author(s): Saito Y., Suzuki T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Role of JIP1b in the fast axonal transport of APP by kinesin-1 in neuron. (2010)
  • Author(s): Araseki M, Nozawa K,(3名略), Kinjo M, Suzuki T.
  • Organizer: The American Society for Cell Biology 50th Annual meeting
  • Place of Presentation: Philadelphia, PA USA
• [Book] Alzheimer's disease as a membrane-associated enzymopathy ofβ-amyloid precursor protein(APP) secretases, in "Lipids and Cellular Membranes in Amyloid Disease" (2011)
  • Author(s): Hata, S., Saito, Y. and Suzuki, T.
  • Publisher: Wiley-VCH
• [Book] Alzheimer's disease as a membrane-associated enzymopathy of β-amyloid precursor protein (APP) secretases, in "Lipids and Cellular Membranes in Amyloid Disease" (Eds by Jelinek, R.) (2011)
  • Author(s): Hata, S., Saito, Y., Suzuki, T.
  • Publisher: Wiley-VCH (ISBN : 978-3-527-32860-4)
• [Book] Lipid and Cellular Membrane in Amyloid Disease "Alzheimer's disease as membrane-associated enzymopathy of APP secretase" (2011)
  • Author(s): Hata S, Saito Y, Suzuki T.
  • Publisher: Willy (editor Raz Jelinek)(In press)
• [Book] Cell Cycle Regulattors in Alzheimer's Disease (Chapter 7 ; Cell cycle regulated phosphorylation of Alzheimer's amyloid precursor protein) (2010)
  • Author(s): Nakaya T, Iijima-Ando K, Suzuki T.
  • Total Pages: 159
  • Publisher: Transworld Research Network (editor Jaya Padmanabhan)
• [Remarks]
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