Mechanism of kinesin-1 activation by cargo receptor

2011 Fiscal Year Final Research Report

• 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
• Keywords: 細胞生物学

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 Pages: 9
  • DOI: doi:10.1186/1750-1326-7-9
  • 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 Pages: e23007
  • DOI: doi:10.1371/journal.pone.0023007
  • Peer Reviewed
• [Journal Article] Intracellular trafficking of amyloid b-protein precursor(APP) regulated by novel function of X11-like (2011)
  • Author(s): Saito, Y., Akiyama, M., Araki, Y., Sumioka, A., Shiono, M., Taru, H., Nakaya, T., Yamamoto, T. and Suzuki, T.
  • Journal Title: PLoS ONE Volume: 6 Pages: e22108
  • DOI: 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] 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
• [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)
  • Year and Date: 20120328-31
• [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)
  • Year and Date: 20111203-07
• [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)
  • Year and Date: 20111203-07
• [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)
  • Year and Date: 20110921-24
• [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)
  • Year and Date: 20110716-21
• [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)
  • Year and Date: 20110716-21
• [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)
  • Year and Date: 20110716-21
• [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)
  • Year and Date: 20110716-21
• [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)
  • Year and Date: 20101211-15
• [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)
  • Year and Date: 20101211-15
• [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)
  • Year and Date: 20101211-15
• [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)
  • Year and Date: 20101105-07
• [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)
  • Year and Date: 20100710-15
• [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)
  • Year and Date: 20100710-15
• [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)
  • Year and Date: 20100710-15
• [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)
  • Year and Date: 20100710-15
• [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.
  • Total Pages: 77-194
  • Publisher: Wiley-VCH
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/shinkei/index.html