Motomasa Tanaka, Ph.D.

Research Overview

We are investigating the molecular basis of neurodegenerative disorders and psychiatric diseases using both in vivo and in vitro systems via a variety of techniques including neurobiology, structural biology, genetics and proteomics. In conjunction, we are seeking to uncover the structural basis of yeast prion strains and transmission barriers, and to identify novel functional prions or protein aggregates that play physiological roles in cells.

Main Research Fields

Biological Sciences

Related Research Fields

Medicine, Dentistry & Pharmacy

Keywords

• Neuropsychiatric disease
• Protein aggregation
• Amyloid
• Nascent chain biology

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 GABA_A 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