Our goal is to elucidate molecular mechanisms of protein aggregation and its physiological consequences in neuropsychiatric diseases.

Motomasa Tanaka

Motomasa Tanaka, Ph.D.

Team Leader, Protein Conformation Diseases
motomasa.tanaka [at] riken.jp

Research Overview

We are investigating the molecular basis of neuropsychiatric diseases using both in vivo and in vitro systems with a variety of techniques including neuroscience, genetics, chemical biology and structural biology. In conjunction, we are seeking to develop novel proteomics or genomics technologies to advance our understanding of the mechanisms of cellular aging and abnormal mRNA translation. Furthermore, we will uncover the structural basis of formation, disaggregation and propagation of amyloid fibers using the yeast prion system that we have established.

Main Research Fields

Biological Sciences

Related Research Fields

Medicine, Dentistry & Pharmacy

Keywords

Selected Publications

  1. Endo R., Chen Y.K., Burke J., Takashima N., Suryawanshi N., Hui K.K., Miyazaki T., Tanaka M.:
    "Dysregulation of ribosome-associated quality control elicits cognitive disorders via overaccumulation of TTC3."
    Proc. Natl. Acad. Sci. U. S. A., 120, e2211522120 (2023).
    10.1073/pnas.2211522120
  2. Nakagawa Y., Shen C-h,, Komi Y., Sugiyama S., Kurinomaru T., Tomabechi Y., Krayukhina E., Okamoto K., Yokoyama T., Shirouzu M., Uchiyama S., Inaba M., Niwa T., Sako Y., Taguchi H., Tanaka M.:
    "Amyloid conformation-dependent disaggregation in a reconstituted yeast prion system."
    Nat. Chem. Biol., 18, 321-331 (2022).
    10.1038/s41589-021-00951-y
  3. Shida T., Kamatari Y.O., Yoda T., Yamaguchi Y., Feig M., Ohhashi Y., Sugita Y., Kuwata K., and Tanaka M.:
    "Short disordered protein segment regulates cross-species transmission of a yeast prion."
    Nat. Chem. Biol. 16, 756-765 (2020) (cover).
    10.1038/s41589-020-0516-y
  4. Sugiyama, S., Tanaka, M.:
    "Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis."
    Proc Natl Acad Sci U. S. A., 116, 8909-8918 (2019).
    10.1073/pnas.1819715116
  5. Hui, K.K., Takashima, N., Watanabe, A., Chater, T.E., Matsukawa, H., Nekooki-Machida, Y., Nilsson, P., Endo, R., Goda, Y., Saido, T.C., Yoshikawa, T., Tanaka., M.:
    "GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior."
    Science Advances, 5(4), eaau8237 (2019).
    10.1126/sciadv.aau8237
  6. Endo R., Takashima N., Nekooki-Machida Y., Komi Y., Hui K.K., Takao M., Akatsu H., Murayama S., Sawa A., and Tanaka M.:
    "TDP-43 and DISC1 Co-Aggregation Disrupts Dendritic Local Translation and Mental Function in FTLD. Biol. Psychiatry, 84, 509-521 (2018)."
    10.1016/j.biopsych.2018.03.008
  7. Chen  C.W., Tanaka M.
    "Genome-Wide Translation Profiling by Ribosome-Bound tRNA Capture." Cell Rep., 23, 608-621 (2018).
    10.1016/j.celrep.2018.03.035
  8. Ohhashi Y., Yamaguchi Y., Kurahashi H., Kamatari Y.O., Sugiyama S., Uluca B., Piechatzek T., Komi Y., Shida T., Müller H., Hanashima S., Heise H., Kuwata K, and Tanaka M.
    "Molecular basis for diversification of yeast prion strain conformation", Proc. Natl. Acad. Sci. U. S. A., 115, 2389-2394 (2018).
    10.1073/pnas.1715483115
  9. Tanaka, M., Ishizuka, K., Nekooki-Machida, Y., Endo, R., Takashima, N., Sasaki, H., Komi, Y., Gathercole, A., Huston, E., Ishii, K., Hui, K.K., Kurosawa, M., Kim, S.H., Nukina, N.,Takimoto, E., Houslay, M.D., and Sawa, A.:
    "Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington's disease."
    J. Clin. Invest., 127, 1438-1450 (2017).
    10.1172/JCI85594
  10. Suzuki, G., Weissman, J.S., and Tanaka, M.:
    "[KIL-d] protein element confers antiviral activity via catastrophic viral mutagenesis."
    Mol. Cell, 60, 651-660 (2015).
    10.1016/j.molcel.2015.10.020

Lab Members

Principal investigator

Motomasa Tanaka
Laboratory Head

Core members

Yusuke Komi
Research Scientist
Ryo Endo
Research Scientist
Kai-Wan Kelvin Hui
Research Scientist
Marek Konrad Krzyzanowski
Research Scientist
Yi-Kai Chen
Visiting Researcher
Yoshiko Nakagawa
Junior Research Associate
Chih-Hao Shen
International Program Associate
Noriko Takashima
Technical Staff I
John William Burke
Technical Staff II