Our goal is to elucidate molecular mechanisms of protein aggregation and its physiological consequences in neuropsychiatric diseases.
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
- Neuropsychiatric disease
- Protein aggregation
- Amyloid
- Nascent chain biology
Selected Publications
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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
News & Media
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Three chaperones coordinate the breakup of amyloid fibrils in yeast
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Protein pileup affects social behaviors through altered brain signaling
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The benefits of misbehaving: prion helps yeast survive environmental stress
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New yeast prion helps cells survive
-Prion proteins may be best known for their role in infectious diseases, but not all of them are destructive, new research shows-
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Effect of yeast prion protein oligomer formation process on infection efficacy clarified
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