2019.4.11

Motomasa TANAKA, Ph.D.
Position
Team Leader (Laboratory Head)Laboratory for Protein Conformation Diseases
RIKEN Center for Brain Science
Hirosawa 2-1, Wako, Saitama 351-0198, Japan
Phone: +81-48-467-6072
E-mail: motomasa.tanaka[at]riken.jp
Education:
1990-1994

Kyoto University, Faculty of Engineering, Japan: B.S.

1994-1996

Kyoto University, Department of Molecular Engineering, Japan: M.S.

1996-1999

Kyoto University, Department of Molecular Engineering, Japan: Ph.D.
(Prof. Isao Morishima)

Employment:
1996 – 1999

JSPS Predoctoral Fellowships (DC1)1999 – 2002

Special Postdoctoral Fellow of Science, RIKEN Brain Science Institute,Japan (Dr. Nobuyuki Nukina)

2002 – 2006

Postdoctoral Fellow, Howard Hughes Medical Institute and University ofCalifornia-San

Francisco,

Departmentof

CellularandMolecular

Pharmacology, USA (Prof. Jonathan Weissman)
2003 – 2005

JSPS Postdoctoral Fellow for Research Abroad (UCSF)

2005 – 2009

PRESTO Researcher, Japan Science and Technology (2005-2006: UCSF)

2006 – 2011

Unit Leader (PI), Tanaka Research Unit, RIKEN Brain Science Institute,Japan

2011 – 2018

Team Leader (PI), Laboratory for Protein Conformation Diseases, RIKEN
Brain Science Institute, Japan2018 – Present

Team Leader (PI), Laboratory for Protein Conformation Diseases, RIKENCenter for Brain Science, Japan

2016– Present

Visiting Professor, Tokyo Medical and Dental University, Japan2018– Present

Visiting Professor (divisional director in RIKEN), Tokyo Medical andDental University, Japan2018– Present

Visiting Professor, Saitama University, Japan1

Award:2008

The Young Scientists' Prize, The Commendation for Science andTechnology by the Minister of Education, Culture, Sports, Science andTechnology, Japan

2013

JSPS (Japan Society for the Promotion of Science) Prize, Japan

List of full publications[Original Articles](1) Sugiyama, S., and 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., in press(2) 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. Sci Adv., 5(4), eaau8237 (2019).
(3) 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).
(4) Chen, C.W. Tanaka, M. Genome-Wide Translation Profiling by Ribosome-BoundtRNA Capture. Cell Rep., 23, 608-621 (2018).
(5) 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., Tanaka, M. Molecular basis for diversification of yeast prion strain conformation.
Proc. Natl. Acad. Sci. U. S. A., 115, 2389-2394 (2018)..
(6) 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., Sawa, A.* Aggregation of scaffolding
protein DISC1 dysregulates phosphodiesterase 4 in Huntington's disease. J. Clin.
Invest., 127, 1438-1450 (2017).

*Corresponding authors(7) Toyoshima, M., Akamatsu, W., Okada, Y., Ohnishi, T., Balan, S., Hisano, Y., Iwayama,Y.,Toyota, T., Matsumoto, T., Itasaka, N., Sugiyama, S., Tanaka, M., Yano, M., Dean, B.,
Okano, H., Yoshikawa, T. Analysis of induced pluripotent stem cells carrying 22q11.2 deletion.
Transl. Psychiatry, 6, e934 (2016).
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(8) 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).
(9) Nilsson, P., Sekiguchi, M., Akagi, T., Izumi, S., Komori, T., Hui, K., Sörgjerd, K., Tanaka, M.,
Saito, T., Iwata, N., Saido, T.C. Autophagy-related protein 7 deficiency in APP transgenic micedecreases Aβ in multivesicular bodies and induces Aβ accumulation in the Golgi. Am. J.
Pathol., 185(2), 305-13 (2015).
(10) Nilsson, P., Loganathan, K., Sekiguchi, M., Matsuba, Y., Hui, K., Tsubuki, S., Tanaka, M..,
Iwata, N., Saito, T., and Saido, T.C. Aβ secretion and plaque formation depend on autophagy.
Cell Reports, 5, 61-69 (2013).

(11) Suzuki G. Shimazu N., and Tanaka, M. A yeast prion, Mod 5, promotes acquired
drug resistance and cell survival under environmental stress. Science, 336,335-339 (2012).
(12) Tonoki, A., Kuranaga, E., Ito, N., Nekooki-Machida, Y., Tanaka, M., Miura, M. Aging causes
distinct characteristics of polyglutamine amyloids in vivo. Genes Cells 16, 557-564 (2011).
(13) Foo, C.K., Ohhashi, Y., Kelly, M.J., Tanaka, M., Weissman, J.S. Radically Different Amyloid
Conformations Dictate the Seeding Specificity of a Chimeric Sup35 Prion. J. Mol. Biol. 408,
1-8 (2011).

(14) Ohhashi Y, Ito K, Toyama BH, Weissman JS, and Tanaka M. Differences in prion
strain conformations result from non-native interactions in a nucleus. Nat. Chem.
Biol. 6, 225-230 (2010).
(15) Nekooki-Machida, Y., Kurosawa, M., Nukina, N., Ito, K., Oda, T., and Tanaka, M.
Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show
different cytotoxicity. Proc. Natl. Acad. Sci. U. S. A., 106, 9678-9684 (2009).
(16) McDobald M., Kendall A., Tanaka M., Weissman JS, Stubbs G. Enclosed chambers forhumidity control and sample containment in fiber diffraction. J. Appl. Cryst., 41, 206-209(2008).
(17) Krzewska J, Tanaka M, Burston SG, Melki R. "Biochemical and functional analysis of theassembly of full-length Sup35p and its prion-forming domain" J. Biol. Chem., 282, 1679-1686(2007).

(18) Tanaka, M., Collins, S.R., Toyama, B.H., and Weissman, J.S. The Physical Basisof How Prion Conformations Determine Strain Phenotypes. Nature, 442, 585-589(2006).
(19) Tanaka, M., Chien, P., Yonekura, K., Weissman, J.S. Mechanism of cross-species
prion transmission: An infectious conformation compatible with two highly divergent
yeast prion proteins. Cell 121, 49-62 (2005).
(20) Venkatraman, P. Wetzel, R. Tanaka, M., Nukina, M., and Goldberg, A.L. Eukaryotic
3Proteasomes Cannot Digest Polyglutamine Sequences and Release Them Intact during
Degradation of Polyglutamine-Containing Proteins. Mol. Cell 14, 95-104 (2004).

(21) Tanaka, M., Chien, P., Naber, N., Cooke, R., and Weissman, J.S. Conformational
Variations in an Infectious Protein Determine Prion Strain Differences. Nature 428,323-328 (2004).
(22) Tanaka, M., Machida, Y., Niu, S., Ikeda, T., Jana, N.R., Doi, H., Kurosawa, M.,Nekooki, M., and Nukina, N. Trehalose alleviates polyglutamine-mediatedpathology in a mouse model of Huntington disease. Nat. Med. 10, 148-154 (2004).
(23) Tanaka, M., Machida, Y., Nishikawa, Y., Akagi, T., Hashikawa, T., Fujisawa, T. and Nukina, N.
Expansion of polyglutamine induces the formation of quasi-aggregate in the early stage ofprotein fibrillization. J. Biol. Chem. 278, 34717–34724 (2003).
(24) Tanaka, M., Matsuura, K., Yoshioka, S., Takahashi, S., Ishimori, K., Hori, H., and Morishima, I.
Activation of Hydrogen Peroxide in Horseradish Peroxidase Occurs within approximately 200
s Observed by a New Freeze-Quench Device. Biophys. J. 84, 1998-2004 (2003).
(25) Tanaka, M., Machida, Y., Nishikawa, Y., Akagi, T., Morishima, I. Hashikawa, T., Fujisawa, T.
and Nukina, N. The Effects of Aggregation-Inducing Motifs on Amyloid Formation of Model
Proteins Related to Neurodegenerative Diseases. Biochemistry 41, 10277-10286 (2002).
(26) Tanaka, M., Morishima, I., Akagi, T., Hashikawa, T. and Nukina, N. Intra-and intermolecularbeta-pleated sheet formation in glutamine-repeat inserted myoglobin as a model forpolyglutamine diseases. J. Biol. Chem. 276, 45470-45475 (2001).
(27) Jana, N.R., Tanaka, M., Wang, G-h., and Nukina, N. Polyglutamine length-dependentinteraction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: theirrole in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 9, 2009-2018 (2000).
(28) Tanaka, M., Ishimori, K. and Morishima, I. Luminol Activity of Horseradish Peroxidase
Mutants Mimicking a Proposed Binding Site for Luminol in Arthromyces ramosus Peroxidase.
Biochemistry 38, 10463-10473 (1999).
(29) Lindgren, A., Tanaka, M., Ruzgas, T., Gorton, L., Gazaryan, I., Ishimori, K. and Morishima, I.
Direct electron transfer catalysed by recombinant forms of horseradish peroxidase: insight into
the mechanism. Electrochem. Commun. 1, 171-175 (1999).
(30) Tanaka, M., Ishimori, K. and Morishima, I. Structural Roles of the Highly Conserved Glu
Residue in the Heme Distal Site of Peroxidases. Biochemistry 37, 2629-2638 (1998).
(31) Morimoto, A., Tanaka, M.Takahashi, S., Ishimori, K., Hori, H., and Morishima, I. Detection ofa Tryptophan Radical as an Intermediate Species in the Reaction of Horseradish Peroxidase
Mutant (Phe-221 -> Trp) and Hydrogen Peroxide. J. Biol. Chem. 273, 14753-14760 (1998).
(32) Tanaka, M., Ishimori, K., Mukai, M., Kitagawa, T., and Morishima, I. Catalytic Activities andStructural Properties of Horseradish Peroxidase Distal His42 -> Glu or Gln Mutant.
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Biochemistry 36, 9889-9898 (1997).
(33) Mukai, M., Nagano, S., Tanaka, M., Ishimori, K., Watanabe, Y., Morishima, I., Ogura, T., andKitagawa, T. Effects of Concerted Hydrogen Bonding Distal Histidine on Active Site Structuresof Horseradish Peroxidase. Resonance Raman Studies with Asn70 Mutants. J. Am. Chem. Soc.,
119, 1758-1766 (1997).
(34) Tanaka, M., Nagano, S., Ishimori, K., Morishima, I. Hydrogen Bond Network in the Distal Siteof Peroxidases: Spectroscopic Properties of Asn70 -> Asp Horseradish Peroxidase Mutant.
Biochemistry 36, 9791-9798 (1997).
(35) Tanaka, M., Ishimori, K. and Morishima, I. The Distal Glutamic Acid as an Acid-Base Catalyst
in the Distal Site of Horseradish Peroxidase. Biochem. Biophys. Res. Commun. 227, 393-399(1996).
(36) Nagano, S., Tanaka, M., Ishimori, K., Watanabe, Y., and Morishima, I. Catalytic Roles of theDistal Site Asparagine-Histidine Couple in Peroxidases. Biochemistry 35, 14251-14258 (1996).
(37) Nagano, S., Tanaka, M., Watanabe, Y., and Morishima, I. Putative Hydrogen Bond Network inthe Heme Distal Site of Horseradish Peroxidase. Biochem. Biophys. Res. Commun. 207,417-423 (1995).
[Reviews and Books](1) Tanaka, M. and Komi, Y. Layers of structure and function in protein aggregation. Nat.
Chem. Biol., 11, 373-377 (2015).
(2) Sugiyama, S. and Tanaka, M. Self-propagating amyloid as a critical regulator for diverse
cellular functions. J. Biochem, 155, 345-351 (2014).
(3) Suzuki G, Tanaka, M. Active conversion to the prion state as a molecular switch for cellular
adaptation to environmental stress. BioEssays, 35, 12-16 (2013).
(4) Suzuki G, Tanaka, M. Expanding the yeast prion world: Active prion conversion ofnon-glutamine/asparagine-rich Mod5 for cell survival. Prion, 7, 109-113 (2013).

(5) Tanaka, M. Tracking a toxic polyglutamine epitope. Nat. Chem. Biol. 7, 861-862(2011).
(6) Tanaka, M. A protein transformation protocol for introducing yeast prion particles into yeast.
Methods in Enzymology (Guide to Yeast Genetics: Functional Genomics, Proteomics and Other
Systems Analysis), 470, 681-693 (2010).
(7) Tanaka, M., and Weissman, J.S. An efficient protein transformation protocol for introducing
prions into yeast. Methods in Enzymology (Amyloid, Prions, and Other Protein Aggregates,Part B), 412, 185-200 (2006).

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(8) Tanaka, M., Machida, Y., and Nukina, N. A novel therapeutic strategy for polyglutamine
diseases by stabilizing aggregation-prone proteins with small molecules. J. Mol. Med. 83,343-352 (2005).
(9) Tanaka, M., Morimoto, A., Ishimori, K., and Morishima, I. Structure-Activity Relation ofHorseradish Peroxidase as Studied with Mutations at Heme Distal and Proximal Sites. Pure &Appl. Chem. 70, 911-916 (1998).
(10) Nagano, S., Tanaka, M., Ishimori, K., Morishima, I., Watanabe, Y., Mukai, M., Ogura, T., andKitagawa, T. Catalytic roles of the distal site hydrogen bond network of peroxidases. Oxygen
Homeostasis and Its Dynamics. Ishimura, Y., Shimada, H., and Suematsu, M. (eds.),
Springer-Verlag; Tokyo, 354 (1997).

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