KIYONAKA LABORATORY Department Of Biomolecular Chemistry, Graduate School of Engineering, Nagoya University


Original Paper

  1. Ojima K., Shiraiwa K., Soga K., Doura T., Takato M., Komatsu K., Yuzaki M., Hamachi I., Kiyonaka S. Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking. Nature Commun. 12, 831 (2021).
  2. Sakamoto S., Yamaura K., Numata T., Harada F., Amaike K., Inoue R., Kiyonaka S., Hamachi I. Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAA Receptor Using a Turn-On Probe. ACS Cent. Sci. 5, 1541-1553 (2019)
  3. Kubota R., Kiyonaka S., Hamachi I. On-cell coordination chemistry: Chemogenetic activation of membrane-bound glutamate receptors in living cells. Methods Enzymol, 622, 411-430 (2019).
  4. Ha H.T.T., Leal-Ortiz S., Lalwani K., Kiyonaka S., Hamachi I., Mysore S.P., Montgomery J.M., Garner C.C., Huguenard J.R., Kim S.A. Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons. Front. Mol. Neurosci., 11, 405 (2018).
  5. Kubota R., Nomura W., Iwasaka T., Ojima K., Kiyonaka S., Hamachi I. Chemogenetic Approach Using Ni(II) Complex-Agonist Conjugates Allows Selective Activation of Class A G-Protein-Coupled Receptors. ACS Cent. Sci., 4, 1211-1221 (2018).
  6. Kiyonaka S., Sakamoto S., Wakayama S., Morikawa Y., Tsujikawa M., Hamachi I. Ligand-directed chemistry of AMPA receptors confers live-cell fluorescent biosensors. ACS Chem. Biol., 13, 1880-1889 (2018).
  7. Kurokawa T., Kiyonaka S., Nakata E., Endo M., Koyama S., Mori E., Tran N.H., Dinh H., Suzuki Y., Hidaka K., Kawata M., Sato C., Sugiyama H., Morii T., Mori Y. DNA origami scaffolds as templates for functional tetrameric Kir3 K+ channels. Angew. Chem. Int. Ed., 57, 2586-2591 (2018).
  8. Tamura T., Song Z., Amaike K., Lee S., Yin S., Kiyonaka S., Hamachi I. Affinity-guided oxime chemistry for selective protein acylation in live tissue systems. J. Am. Chem. Soc., 139, 14181-14191 (2017).
  9. Yamaura K., Kiyonaka S., Hamachi I. Construction of protein-based biosensors using ligand-directed chemistry for detecting analyte binding. Methods Enzymol., 589, 253-280 (2017).
  10. Wakayama S., Kiyonaka S., Arai I., Kakegawa W., Matsuda S., Ibata K., Nemoto L.Y., Kusumi A., Yuzaki M., Hamachi I. Chemical labeling for visualizing native AMPA receptors in live neurons. Nature Commun., 8, 14850 (2017).
  11. Miki T., Awa M., Nishikawa Y., Kiyonaka S., Wakabayashi M., Ishihama Y., Hamachi I. A conditional proteomics approach to identify proteins involved in zinc homeostasis. Nature Methods, 13, 931-937 (2016).
  12. Kiyonaka S., Kubota R., Michibata Y., Sakakura M., Takahashi H., Numata T., Inoue R., Yuzaki M., Hamachi I. Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells. Nature Chem., 8, 958-967 (2016).
  13. Yamaura K., Kiyonaka S., Numata T., Inoue R., Hamachi I. Discovery of allosteric modulators for GABAA receptors by ligand-directed chemistry. Nature Chem. Biol., 12, 822-830 (2016).
  14. Yasueda Y., Tamura T., Fujisawa A., Kuwata K., Tsukiji S., Kiyonaka S., Hamachi I. A set of organelle-localizable reactive molecules for mitochondrial chemical proteomics in living cells and brain tissues. J. Am. Chem. Soc., 138, 7592-7602 (2016).
  15. Sawamura S., Hatano M., Takada Y., Hino K., Kawamura T., Tanikawa J., Nakagawa H., Hase H., Nakao A., Hirano M., Rotrattanadumrong R., Kiyonaka S., Mori M.X., Nishida M., Hu Y., Inoue R., Nagata R., Mori Y. Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds. Mol. Pharmacol., 89, 348-363 (2016).
  16. Nagamori S., Wiriyasermkul P., Okuda S., Kojima N., Hari Y., Kiyonaka S., Mori Y., Tominaga H., Ohgaki R., Kanai Y. Structure-activity relations of leucine derivatives reveal critical moieties for cellular uptake and activation of mTORC1-mediated signaling. Amino Acids, 48,1048-1058 (2016).
  17. Takada Y., Hirano M., Kiyonaka S., Ueda Y., Yamaguchi K., Nakahara K., Mori M.X., Mori Y. Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels. Cell Calcium, 58, 296-306 (2015).
  18. Nakao A., Miki T., Shimono K., Oka H., Numata T., Kiyonaka S., Matsushita K., Ogura H., Niidome T., Noebels J.L., Wakamori M., Imoto K., Mori Y. Compromised maturation of GABAergic inhibition underlies abnormal network activity in the hippocampus of epileptic Ca2+ channel mutant mice, tottering. Pflugers Arch., 467, 737-752 (2015).
  19. Takahashi N., Hamada-Nakahara S., Itoh Y., Takemura K., Shimada A., Ueda Y., Kitamata M., Matsuoka R., Hanawa-Suetsugu K., Senju Y., Mori M.X., Kiyonaka S., Kohda D., Kitao A., Mori Y., Suetsugu S. TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2. Nature Commun., 25, 4994 (2014).
  20. Yamada Y., Kinoshita H., Kuwahara K., Nakagawa Y., Kuwabara Y., Minami T., Yamada C., Shibata J., Nakao K., Cho K., Arai Y., Yasuno S., Nishikimi T., Ueshima K., Kamakura S., Nishida M., Kiyonaka S., Mori Y., Kimura T., Kangawa K., Nakao K. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure. Cardiovasc. Res., 104, 183-193 (2014).
  21. Yamaura K., Kuwata K., Tamura T., Kioi Y., Takaoka Y., Kiyonaka S., Hamachi I. Live cell off-target identification of lapatinib using ligand-directed tosyl chemistry. Chem. Commun., 50, 14097-14100 (2014).
  22. Miki T., Fujishima S., Komatsu K., Kuwata K., Kiyonaka S., Hamachi I. LDAI-based chemical labeling of intact membrane proteins and its pulse-chase analysis under live cell conditions. Chem. Biol., 21, 1013-1022 (2014).
  23. Kozai D., Kabasawa Y., Ebert M., Kiyonaka S., Firman, Otani Y., Numata T., Takahashi N., Mori Y., Ohwada T. Transnitrosylation directs TRPA1 selectivity in N-nitrosamine activators. Mol. Pharmacol., 85, 175-185 (2014).
  24. Kiyonaka S., Kajimoto T., Sakaguchi R., Shinmi D., Omatsu-Kanbe M., Matsuura H., Imamura H., Yoshizaki T., Hamachi I., Morii T., Mori Y. Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells. Nature Methods, 10, 1232-1238 (2013).
  25. Shi J., Geshi N., Takahashi S., Kiyonaka S., Ichikawa J., Hu Y., Mori Y., Ito Y., Inoue R. Molecular determinants for cardiovascular TRPC6 channel regulation by Ca2+/calmodulin-dependent kinase II. J. Physiol., 591, 2851-2866 (2013).
  26. Ronjat M., Kiyonaka S., Barbado M., De Waard M., Mori Y. Nuclear life of the voltage-gated Cacnb4 subunit and its role in gene transcription regulation. Channels, 7, 119-225 (2013).
  27. Ochi R., Kurotani K., Ikeda M., Kiyonaka S., Hamachi I. Supramolecular hydrogels based on bola-amphiphilic glycolipids showing color change in response to glycosidases. Chem. Commun., 49, 2115-2117 (2013).
  28. Tadmouri A., Kiyonaka S., Barbado M., Rousset M., Fablet K., Sawamura S., Bahembera E., Pernet-Gallay K., Arnoult C., Miki T., Sadoul K., Gory-Faure S., Lambrecht C., Lesage F., Akiyama S., Khochbin S., Baulande S., Janssens V., Andrieux A., Dolmetsch R., Ronjat M., Mori Y., De Waard M. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. EMBO J., 31, 3730-3744 (2012).
  29. Kiyonaka S., Nakajima H., Takada Y., Hida Y., Yoshioka T., Hagiwara A., Kitajima I., Mori Y., Ohtsuka T. Physical and functional interaction of the active zone protein CAST/ERC2 and the β-subunit of the voltage-dependent Ca2+ channel. J. Biochem., 152, 149-159 (2012).
  30. Nakata M., Liew F.F., Uwatoko C., Kiyonaka S., Mori Y., Katsuda Y., Endo M., Sugiyama H., Morii M. Zinc-finger proteins for site-specific protein positioning on DNA origami structures. Angew. Chem. Int. Ed., 51, 2421-2424 (2012).
  31. Katano M., Numata T., Aguan K., Hara Y., Kiyonaka S., Yamamoto S., Miki T., Sawamura S., Suzuki T., Yamakawa K., Mori Y. The juvenile myoclonic epilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death. Cell Calcium, 51, 179-185 (2012).
  32. Takahashi N., Kuwaki T., Kiyonaka S., Numata T., Kozai D., Mizuno Y., Yamamoto S., Naito S., Knevels E., Carmeliet P., Oga T., Kaneko S., Suga S., Nokami T., Yoshida J., Mori Y. TRPA1 underlies a sensing mechanism for O2. Nature Chem. Biol., 7, 701-711 (2011).
  33. Wang H., Koshi Y., Minato D., Nonaka H., Kiyonaka S., Mori Y., Tsukiji S., Hamachi I. Chemical cell-surface receptor engineering using affinity-guided, multivalent organocatalysts. J. Am. Chem. Soc., 133, 12220-12228 (2011).
  34. Kitajima N., Watanabe K., Morimoto S., Sato Y., Kiyonaka S., Hoshijima M., Ikeda Y., Nakaya M., Ide T., Mori Y., Kurose H., Nishida M. TRPC3-mediated Ca2+ influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts. Biochem. Biophys. Res. Commun., 409, 108-113 (2011).
  35. Kim M.S., Lee K.P., Yang D., Shin D.M., Abramowitz J., Kiyonaka S., Birnbaumer L., Mori Y., Muallem S. Genetic and pharmacologic inhibition of the Ca2+ influx channel TRPC3 protects secretory epithelia from Ca2+-dependent toxicity. Gastroenterology, 140, 2107-2115 (2011).
  36. Weiss N., Sandoval A., Kiyonaka S., Felix R., Mori Y., De Waard M. Rim1 modulate direct G-protein regulation of Cav2.2 channels. Pflugers Arch., 461, 447-459 (2011).
  37. Uriu Y., Kiyonaka S., Miki T., Yagi M., Akiyama S., Mori E., Nakao A., Beedle A.M., Campbell K.P., Wakamori M., Mori Y. RIMγ isoforms lacking the Rab3-binding domain induce long-lasting currents but block neurotransmitter vesicle-anchoring in voltage-dependent P/Q-type Ca2+ channels. J. Biol. Chem., 285, 21750-21767 (2010).
  38. Kinoshita H., Kuwahara K., Nishida M., Jiang Z., Rong X., Kiyonaka S., Kuwabara Y., Kurose H., Inoue R., Mori Y., Li Y., Nakagawa Y., Usami S., Fujiwara M., Yamada Y., Minami T., Ueshima K., Nakao K. Inhibition of TRPC6 channel activity contributes to the antihypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart. Circ. Res., 106, 1849-1860 (2010).
  39. Sakaguchi R., Tainaka K., Shimada N., Nakano S., Inoue M., Kiyonaka S., Mori Y., Morii T. An in vivo fluorescent sensor reveals intracellular Ins(1,3,4,5)P4 dynamics in single cells. Angew. Chem. Int. Ed., 49, 2150-2153 (2010).
  40. Numaga T., Nishida M., Kiyonaka S., Kato K., Katano M., Mori E., Kurosaki T., Inoue R., Hikida M., Putney Jr J.W., Mori Y. Ca2+ influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells. J. Cell Sci., 123, 927-938 (2010).
  41. Watanabe H., Yamashita T., Saitoh N., Kiyonaka S., Iwamatsu A., Campbell K.P., Mori Y., Takahashi T. Involvement of Ca2+ channel synprint site in synaptic vesicle endocytosis. J. Neurosci., 30, 655-660 (2010).
  42. Miyagi K., Kiyonaka S., Yamada K., Miki T., Mori E., Kato K., Numata T., Sawaguchi Y., Numaga T., Kimura T., Kanai Y., Kawano M., Wakamori M., Nomura H., Koni I., Yamagishi M., Mori Y. A pathogenic C-terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. J. Biol. Chem., 284, 34400-34412 (2009).
  43. Kato K., Kiyonaka S., Sawaguchi Y., Tohnishi M., Masaki T., Yasokawa N., Mizuno Y., Mori E., Inoue K., Hamachi I., Takeshima H., Mori Y. Molecular characterization of flubendiamide sensitivity in lepidopterous ryanodine receptor Ca2+ release channel. Biochemistry, 48, 10342-10352 (2009).
  44. Sakaguchi R., Endo T., Yamamoto S., Tainaka K., Sugimoto K., Fujieda N., Kiyonaka S., Mori Y., Morii T. A single circularly permuted GFP sensor for inositol-1,3,4,5-tetrakisphosphate based on a split PH domain. Bioorg. Med. Chem., 17, 7381-7386 (2009).
  45. Sun H.S., Jackson M.F., Martin L.J., Jansen K., Teves L., Cui H., Kiyonaka S., Mori Y., Jones M., Forder J.P., Golde T.E., Orser B.A., Macdonald J.F., Tymianski M. Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nature Neurosci., 12, 1300-1307 (2009).
  46. Maruyama Y., Ogura T., Mio K., Kato K., Kaneko T., Kiyonaka S., Mori Y., Sato C. Tetrameric Orai1 is a teardrop-shaped molecule with a long, tapered cytoplasmic domain. J. Biol. Chem., 284, 13676-13685 (2009).
  47. Kiyonaka S., Kato K., Nishida M., Mio K., Numaga T., Sawaguchi Y., Yoshida T., Wakamori M., Mori E., Numata T., Ishii M., Takemoto H., Ojida A., Watanabe K., Uemura A., Kurose H., Morii T., Kobayashi T., Sato Y., Sato C., Hamachi I., Mori Y. Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc. Natl. Acad. Sci. USA, 106, 5740-5745 (2009).
  48. Takeuchi K., Nakano Y., Kato U., Kaneda M., Aizu M., Awano W., Yonemura S., Kiyonaka S., Mori Y., Yamamoto D., Umeda M. Changes in temperature preferences and energy homeostasis in dystroglycan mutants. Science, 323, 1740-1743 (2009).
  49. Olah M.E., Jackson M.F., Li H., Perez Y., Sun H.S., Kiyonaka S., Mori Y., Tymianski M., Macdonald J.F. Ca2+-dependent induction of TRPM2 currents in hippocampal neurons. J. Physiol., 587, 965-979 (2009).
  50. Ohmori I., Ouchida M., Miki T., Mimaki N., Kiyonaka S., Nishiki T., Tomizawa K., Mori Y., Matsui H. A CACNB4 mutation shows that altered Cav2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy. Neurobiol. Dis., 32, 349-354 (2008).
  51. Takahashi N., Mizuno Y., Kozai D., Yamamoto S., Kiyonaka S., Shibata T., Uchida K., Mori Y. Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels, 2, 287-298 (2008).
  52. Yamamoto S., Shimizu S., Kiyonaka S., Takahashi N., Wajima T., Hara Y., Negoro T., Hiroi T., Kiuchi Y., Okada T., Kaneko S., Lange I., Fleig A., Penner R., Nishi M., Takeshima H., Mori Y. TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nature Med., 14, 738-747 (2008).
  53. Maruyama Y., Ogura T., Mio K., Kiyonaka S., Kato K., Mori Y., Sato C. Three-dimensional reconstruction using transmission electron microscopy reveals a swollen, bell-shaped structure of transient receptor potential melastatin type 2 cation channel. J. Biol. Chem., 282, 36961-36970 (2007).
  54. Mio K., Ogura T., Kiyonaka S., Mori Y., Sato C. Subunit dissociation of TRPC3 ion channel under high-salt condition. J. Electron Microsc., 56, 111-117 (2007).
  55. Miki T., Kiyonaka S., Uriu Y., De Waard M., Wakamori M., Beedle A.M., Campbell K.P., Mori Y. Mutation associated with an autosomal dominant cone-rod dystrophy CORD7 modifies RIM1-mediated modulation of voltage-dependent Ca2+ channels. Channels, 1 144-147 (2007).
  56. Kiyonaka S., Wakamori M., Miki T., Uriu Y., Nonaka M., Bito H., Beedle A.M., Mori E., Hara Y., De Waard M., Kanagawa M., Itakura M., Takahashi M., Campbell K.P., Mori Y. RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels. Nature Neurosci., 10, 691-701 (2007).
  57. Mio K., Ogura T., Kiyonaka S., Hiroaki Y., Tanimura Y., Fujiyoshi Y., Mori Y., Sato C. The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas.J. Mol. Biol., 367, 373-383 (2007).
  58. Yamazaki K., Shigetomi E., Ikeda R., Nishida M., Kiyonaka S., Mori Y., Kato F. Blocker-resistant presynaptic voltage-dependent Ca2+ channels underlying glutamate release in mice nucleus tractus solitarii. Brain Res., 1104, 103-113 (2006).
  59. Ojida A., Honda K., Shinmi D., Kiyonaka S., Mori Y., Hamachi I. Oligo-Asp tag/Zn(II) complex probe as a new pair for labeling and fluorescence imaging of proteins. J. Am. Chem. Soc., 128, 10452-10459 (2006).
  60. Tamaru S., Kiyonaka S., Hamachi I. Three distinct read-out modes for enzyme activity can operate in a semi-wet supramolecular hydrogel. Chem. Eur. J., 11, 7294-7304 (2005).
  61. Zhou S.-L., Matsumoto S., Tian H.-D., Yamane H., Ojida A., Kiyonaka S., Hamachi I. pH-responseive shrinkage/swelling of a supramolecular hydrogel composed of two small amphiphilic molecules. Chem. Eur. J., 11, 1130-1136 (2005).
  62. Aiba Y., Oh-hora M., Kiyonaka S., Kimura Y., Hikita A., Mori Y., Kurosaki T. Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation. Proc. Natl. Acad. Sci. USA, 101,16612-16617 (2004).
  63. Kiyonaka S., Sada K., Yoshimura I., Shinkai S., Kato N., Hamachi I. Semi-wet peptide/protein array using supramolecular hydrogel. Nature Mater., 3, 58-64 (2004).
  64. Kiyonaka S., Zhou S.-L., Hamachi I. pH-responsive phase transition of supramolecular hydrogel consisting of glycosylated amino acetate and carboxylic acid derivative. Supramolecular Chem., 15, 521-528 (2003).
  65. Kiyonaka S., Shinkai S., Hamachi I. Combinatorial library of low molecular-weight organo- and hydrogelators based on glycosylated aminoacid derivatives by solid-phase synthesis. Chem. Eur. J., 9, 976-984 (2003).
  66. Kiyonaka S., Sugiyasu K., Shinkai S., Hamachi I. First thermally responsive supramolecular polymer based on glycosylated amino acid. J. Am. Chem. Soc., 124, 10954-10955 (2002).
  67. Bewley C.A., Kiyonaka S., Hamachi I. Site-specific discrimination by cyanovirin-N for α-linked trisaccharides comprising the three arms of man8 and man9. J. Mol. Biol., 322, 881-889 (2002).
  68. Hamachi I., Kiyonaka S., Shinkai S. Solid-phase lipid synthesis (SPLS)-2: incidental discovery of organogelators based on artificial glycolipids. Tetrahedron Lett., 42, 6141-6145 (2001).
  69. Hamachi I., Kasagi N., Kiyonaka S., Nagase T., Mito-oka Y., Shinkai S. Pd(en) as a sequence-selective molecular pinch for α-helical peptides. Chem. Lett., 16-17 (2001).
  70. Murakami H., Okusa Y., Kiyonaka S., Hamachi I., Shinkai S., Nakashima N. The synthesis of a reconstituted C60-modified protein. Chem. Lett., 46-47 (2000).
  71. Hamachi I., Kiyonaka S., Shinkai S. Solid-phase lipid synthesis (SPLS) for construction of an artificial glycolipid library. Chem. Commun., 1281-1282 (2000).
  72. Inoue K., Ono Y., Kanekiyo Y., Kiyonaka S., Hamachi I., Shinkai S. Facile preparation of robust organic gels by cross-link of a sugar-integrated getator by toluene-2,4-diisocyanate. Chem. Lett., 255-256 (1999).

English review or commentary

  1. Sakamoto S, Kiyonaka S, Hamachi I. Construction of ligand assay systems by protein-based semisynthetic biosensors. Curr. Opin. Chem. Biol., 50, 10-18 (2019).
  2. Okabe K., Sakaguchi R., Shi B., Kiyonaka S. Intracellular thermometry with fluorescent sensors for thermal biology. Pflugers Arch., 470, 717-731 (2018).
  3. Mori Y., Takahashi N., Kurokawa T., Kiyonaka S. TRP channels in oxygen physiology: distinctive functional properties and roles of TRPA1 in O2 sensing. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci., 93, 464-482 (2017).
  4. Kiyonaka S., Sakaguchi R., Hamachi I., Morii T., Yoshizaki T., Mori Y. Validating subcellular thermal changes revealed by fluorescent thermosensors. Nature Methods, 12, 801-802 (2015).
  5. Sakaguchi R., Kiyonaka S., Mori Y. Fluorescent sensors reveal subcellular thermal changes. Curr. Opin. Biotechnol., 31, 57-64 (2015).
  6. Mori Y., Kiyonaka S., Kanai Y. Transportsomes and channelsomes: are they functional units for physiological responses? Channels, 5, 387-390 (2011).
  7. Numata T., Kiyonaka S., Kato K., Takahashi N., Mori Y. Activation of TRP channels in mammalian systems. TRP Channels, Taylor & Francis, 43-90 (2011).
  8. Mori Y., Kajimoto T., Nakao A., Takahashi N., Kiyonaka S. Receptor signaling integration by TRP channelsomes. Transient Receptor Potential Channels, Springer, 373-389 (2011).