Researcher basic information

• Ph.D., The University of Tokyo

• https://researchmap.jp/taru?lang=en

• 30533731

• https://orcid.org/0000-0002-3773-2614

• 201001039942066468

• 老化
• 神経変性疾患
• 線虫
• C. elegans
• シナプス
• 神経

• Life Science, Developmental biology
• Life Science, Cell biology
• Life Science, Neuroscience-general
• Life Science, Pharmaceutical hygiene and biochemistry

• Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy
• Master's degree program, Graduate School of Life Science
• Doctoral (PhD) degree program, Graduate School of Life Science

Research activity information

• Suppression of the amyloidogenic metabolism of APP and the accumulation of Aβ by alcadein α in the brain during aging.
  Keiko Honda; Hiroo Takahashi; Saori Hata; Ruriko Abe; Takashi Saito; Takaomi C Saido; Hidenori Taru; Yuriko Sobu; Kanae Ando; Tohru Yamamoto; Toshiharu Suzuki
  Scientific reports, 14, 1, 18471, 18471, 09 Aug. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Generation and accumulation of amyloid-β (Aβ) protein in the brain are the primary causes of Alzheimer's disease (AD). Alcadeins (Alcs composed of Alcα, Alcβ and Alcγ family) are a neuronal membrane protein that is subject to proteolytic processing, as is Aβ protein precursor (APP), by APP secretases. Previous observations suggest that Alcs are involved in the pathophysiology of Alzheimer's disease (AD). Here, we generated new mouse AppNL-F (APP-KI) lines with either Alcα- or Alcβ-deficient background and analyzed APP processing and Aβ accumulation through the aging process. The Alcα-deficient APP-KI (APP-KI/Alcα-KO) mice enhanced brain Aβ accumulation along with increased amyloidogenic β-site cleavage of APP through the aging process whereas Alcβ-deficient APP-KI (APP-KI/Alcβ-KO) mice neither affected APP metabolism nor Aβ accumulation at any age. More colocalization of APP and BACE1 was observed in the endolysosomal pathway in neurons of APP-KI/Alcα-KO mice compared to APP-KI and APP-KI/Alcβ-KO mice. These results indicate that Alcα plays an important role in the neuroprotective function by suppressing the amyloidogenic cleavage of APP by BACE1 in the brain, which is distinct from the neuroprotective function of Alcβ, in which p3-Alcβ peptides derived from Alcβ restores the viability in neurons impaired by toxic Aβ.
• Axonal transport of Frizzled5 by Alcadein α-containing vesicles is associated with kinesin-1.
  Yuzuha Shiraki; Monet Mitsuma; Ritsuko Takada; Saori Hata; Akira Kitamura; Shinji Takada; Masataka Kinjo; Hidenori Taru; Ulrike C Müller; Tohru Yamamoto; Yuriko Sobu; Toshiharu Suzuki
  Molecular biology of the cell, 34, 11, ar110, 01 Oct. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Alcadein α (Alcα) and amyloid-β protein precursor (APP) are cargo receptors that associate vesicles with kinesin-1. These vesicles, which contain either Alcα or APP, transport various proteins/cargo molecules into axon nerve terminals. Here, we analyzed immune-isolated Alcα- and APP-containing vesicles of adult mouse brains with LC-MS/MS and identified proteins present in vesicles that contained either Alcα or APP. Among these proteins, Frizzled-5 (Fzd5), a Wnt receptor, was detected mainly in Alcα vesicles. Although colocalization ratios of Fzd5 with Alcα are low in the neurites of differentiating neurons by a low expression of Fzd5 in embryonic brains, the suppression of Alcα expression decreased the localization of Fzd5 in neurites of primary cultured neurons. Furthermore, Fzd5-EGFP expressed in primary cultured neurons was preferentially transported in axons with the transport velocities of Alcα vesicles. In synaptosomal fractions of adult-mice brains that express higher levels of Fzd5, the amount of Fzd5 and the phosphorylation level of calcium/calmodulin-dependent protein kinase-II were reduced in the Alcα-deficient mice. These results suggest that reduced transport of Fzd5 by Alcα-containing vesicles associated with kinesin-1 in axon terminals may impair the response to Wnt ligands in the noncanonical Ca2+-dependent signal transduction pathway at nerve terminals of mature neurons.
• Brain p3-Alcβ peptide restores neuronal viability impaired by Alzheimer's amyloid β-peptide.
  Saori Hata; Haruka Saito; Takeharu Kakiuchi; Dai Fukumoto; Shigeyuki Yamamoto; Kensaku Kasuga; Ayano Kimura; Koichi Moteki; Ruriko Abe; Shungo Adachi; Shoich Kinoshita; Kumiko Yoshizawa-Kumagaye; Hideki Nishio; Takashi Saito; Takaomi C Saido; Tohru Yamamoto; Masaki Nishimura; Hidenori Taru; Yuriko Sobu; Hiroyuki Ohba; Shingo Nishiyama; Norihiro Harada; Takeshi Ikeuchi; Hideo Tsukada; Yasuomi Ouchi; Toshiharu Suzuki
  EMBO molecular medicine, 15, 5, e17052, 30 Mar. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3-Alcβ37 is generated from the neuronal protein alcadein β through cleavage of γ-secretase, similar to the generation of amyloid β (Aβ) derived from Aβ-protein precursor/APP. Neurotoxicity by Aβ oligomers (Aβo) is the prime cause prior to the loss of brain function in AD. We found that p3-Alcβ37 and its shorter peptide p3-Alcβ9-19 enhanced the mitochondrial activity of neurons and protected neurons against Aβo-induced toxicity. This is due to the suppression of the Aβo-mediated excessive Ca2+ influx into neurons by p3-Alcβ. Successful transfer of p3-Alcβ9-19 into the brain following peripheral administration improved the mitochondrial viability in the brain of AD mice model, in which the mitochondrial activity is attenuated by increasing the neurotoxic human Aβ42 burden, as revealed through brain PET imaging to monitor mitochondrial function. Because mitochondrial dysfunction is common in the brain of AD patients alongside increased Aβ and reduced p3-Alcβ37 levels, the administration of p3-Alcβ9-19 may be a promising treatment for restoring, protecting, and promoting brain functions in patients with AD.
• Accumulation of amyloid-β in the brain of mouse models of Alzheimer's disease is modified by altered gene expression in the presence of human apoE isoforms during aging.
  Keiko Honda; Yuhki Saito; Haruka Saito; Megumi Toyoda; Ruriko Abe; Takashi Saito; Takaomi C Saido; Makoto Michikawa; Hidenori Taru; Yuriko Sobu; Saori Hata; Tadashi Nakaya; Toshiharu Suzuki
  Neurobiology of aging, 123, 63, 74, Mar. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Apolipoprotein E4 (apoE4) is a risk factor for Alzheimer's disease (AD). Here, we investigated brain amyloid-β (Aβ) accumulation throughout the aging process in an amyloid precursor protein (APP) knock-in (KI) mouse model of AD that expresses human APPNL-G-F with or without human apoE4 or apoE3. Brain Aβ42 levels were significantly lower in 9-month-old mice that express human isoforms of apoE than in age-matched APP-KI control mice. Linear accumulation of Aβ42 began in 5-month-old apoE4 mice, and a strong increase in Aβ42 levels was observed in 21-month-old apoE3 mice. Aβ42 levels in cerebroventricular fluid were higher in apoE3 than in apoE4 mice at 6-7 months of age, suggesting that apoE3 is more efficient at clearing Aβ42 than apoE4 at these ages. However, apoE3 protein levels were lower than apoE4 protein levels in the brains of 21-month-old apoE3 and apoE4 mice, respectively, which may explain the rapid increase in brain Aβ42 burden in apoE3 mice. We identified genes that were downregulated in a human apoE-dependent (apoE4 > apoE3) and age-dependent (apoE3 = apoE4) manner, which may regulate brain Aβ burden and/or AD progression. Analysis of gene expression in AD mouse models helps identify molecular mechanisms of pleiotropy by the human APOE gene during aging.
• Suppression of amyloid-β secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid.
  Saori Hata; Kuniyuki Kano; Kazunori Kikuchi; Shoichi Kinoshita; Yuriko Sobu; Haruka Saito; Takashi Saito; Takaomi C Saido; Yoshitake Sano; Hidenori Taru; Junken Aoki; Hiroto Komano; Taisuke Tomita; Shunji Natori; Toshiharu Suzuki
  Journal of neurochemistry, 159, 3, 603, 617, Nov. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Two common conjugated linoleic acids (LAs), cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid-β (Aβ) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of Aβ in mouse neurons. CLA treatment did not affect the level of β-site APP-cleaving enzyme 1 (BACE1), a component of active γ-secretase complex presenilin 1 amino-terminal fragment, or Aβ protein precursor (APP) in cultured neurons. BACE1 and γ-secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA-containing phosphatidylcholine (CLA-PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane-associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent Aβ generation. Our findings suggest that the accumulation of c9,t11 CLA-PC/LPC in neuronal membranes suppresses the production of neurotoxic Aβ in neurons.
• Enhanced amyloid-β generation by γ-secretase complex in DRM microdomains with reduced cholesterol levels.
  Saori Hata; Anqi Hu; Yi Piao; Tadashi Nakaya; Hidenori Taru; Maho Morishima-Kawashima; Shigeo Murayama; Masaki Nishimura; Toshiharu Suzuki
  Human molecular genetics, 29, 3, 382, 393, 01 Feb. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• RIMB-1/RIM-Binding Protein and UNC-10/RIM Redundantly Regulate Presynaptic Localization of the Voltage-Gated Calcium Channel inCaenorhabditis elegans
  Yuto Kushibiki; Toshiharu Suzuki; Yishi Jin; Hidenori Taru
  The Journal of Neuroscience, 30 Oct. 2019, [Peer-reviewed], [Corresponding author]
  Scientific journal
• The cytoplasmic region of the amyloid β-protein precursor (APP) is necessary and sufficient for the enhanced fast velocity of APP transport by kinesin-1.
  Maoko Tsukamoto; Kyoko Chiba; Yuriko Sobu; Yuzuha Shiraki; Yuka Okumura; Saori Hata; Akira Kitamura; Tadashi Nakaya; Seiichi Uchida; Masataka Kinjo; Hidenori Taru; Toshiharu Suzuki
  FEBS letters, 592, 16, 2716, 2724, Aug. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Phosphorylation of KLC1 modifies interaction with JIP1 and abolishes the enhanced fast velocity of APP transport by kinesin-1.
  Kyoko Chiba; Ko-Yi Chien; Yuriko Sobu; Saori Hata; Shun Kato; Tadashi Nakaya; Yasushi Okada; Angus C Nairn; Masataka Kinjo; Hidenori Taru; Rong Wang; Toshiharu Suzuki
  Molecular biology of the cell, 28, 26, 3857, 3869, 15 Dec. 2017, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans.
  Hisako Nakagawa; Takuya Shiozaki; Eiji Kobatake; Tomohiro Hosoya; Tomohiro Moriya; Fumihiko Sakai; Hidenori Taru; Tadaaki Miyazaki
  Aging cell, 15, 2, 227, 36, Apr. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase.
  Yan Xu; Hidenori Taru; Yishi Jin; Christopher C Quinn
  PLoS genetics, 11, 4, e1005185, Apr. 2015, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Cytoplasmic fragment of Alcadein α generated by regulated intramembrane proteolysis enhances amyloid β-protein precursor (APP) transport into the late secretory pathway and facilitates APP cleavage.
  Norio Takei; Yuriko Sobu; Ayano Kimura; Satomi Urano; Yi Piao; Yoichi Araki; Hidenori Taru; Tohru Yamamoto; Saori Hata; Tadashi Nakaya; Toshiharu Suzuki
  The Journal of biological chemistry, 290, 2, 987, 95, 09 Jan. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.
  Kyoko Chiba; Masahiko Araseki; Keisuke Nozawa; Keiko Furukori; Yoichi Araki; Takahide Matsushima; Tadashi Nakaya; Saori Hata; Yuhki Saito; Seiichi Uchida; Yasushi Okada; Angus C Nairn; Roger J Davis; Tohru Yamamoto; Masataka Kinjo; Hidenori Taru; Toshiharu Suzuki
  Molecular biology of the cell, 25, 22, 3569, 80, 05 Nov. 2014, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Increased levels of plasma p3-alcα35, a major fragment of Alcadeinα by γ-secretase cleavage, in Alzheimer's disease.
  Chiori Omori; Madoka Kaneko; Etsuko Nakajima; Hiroyasu Akatsu; Masaaki Waragai; Masahiro Maeda; Maho Morishima-Kawashima; Yuhki Saito; Tadashi Nakaya; Hidenori Taru; Tohru Yamamoto; Takashi Asada; Saori Hata; Toshiharu Suzuki
  Journal of Alzheimer's disease : JAD, 39, 4, 861, 70, 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Liprin-α/SYD-2 determines the size of dense projections in presynaptic active zones in C. elegans.
  Maike Kittelmann; Jan Hegermann; Alexandr Goncharov; Hidenori Taru; Mark H Ellisman; Janet E Richmond; Yishi Jin; Stefan Eimer
  The Journal of cell biology, 203, 5, 849, 63, 09 Dec. 2013, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Mechanism of intramembrane cleavage of alcadeins by γ-secretase.
  Yi Piao; Ayano Kimura; Satomi Urano; Yuhki Saito; Hidenori Taru; Tohru Yamamoto; Saori Hata; Toshiharu Suzuki
  PloS one, 8, 4, e62431, Apr. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• The Liprin homology domain is essential for the homomeric interaction of SYD-2/Liprin-α protein in presynaptic assembly.
  Hidenori Taru; Yishi Jin
  The Journal of neuroscience : the official journal of the Society for Neuroscience, 31, 45, 16261, 8, 09 Nov. 2011, [Peer-reviewed], [Lead author, Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Intracellular trafficking of the amyloid β-protein precursor (APP) regulated by novel function of X11-like.
  Yuhki Saito; Mayu Akiyama; Yoichi Araki; Akio Sumioka; Maki Shiono; Hidenori Taru; Tadashi Nakaya; Tohru Yamamoto; Toshiharu Suzuki
  PloS one, 6, 7, e22108, 2011, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain.
  Maho Kondo; Maki Shiono; Genzo Itoh; Norio Takei; Takahide Matsushima; Masahiro Maeda; Hidenori Taru; Saori Hata; Tohru Yamamoto; Yuhki Saito; Toshiharu Suzuki
  Molecular neurodegeneration, 5, 1, 35, 35, 15 Sep. 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Phosphorylation of the amino-terminal region of X11L regulates its interaction with APP.
  Megumi Sakuma; Emi Tanaka; Hidenori Taru; Susumu Tomita; Sam Gandy; Angus C Nairn; Tadashi Nakaya; Tohru Yamamoto; Toshiharu Suzuki
  Journal of neurochemistry, 109, 2, 465, 75, Apr. 2009, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Regulation of the physiological function and metabolism of AbetaPP by AbetaPP binding proteins.
  Hidenori Taru; Toshiharu Suzuki
  Journal of Alzheimer's disease : JAD, 18, 2, 253, 65, 2009, [Peer-reviewed], [Invited], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal
• The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport.
  Yoichi Araki; Takanori Kawano; Hidenori Taru; Yuhki Saito; Sachiyo Wada; Kanako Miyamoto; Hisako Kobayashi; Hiroyuki O Ishikawa; Yu Ohsugi; Tohru Yamamoto; Kenji Matsuno; Masataka Kinjo; Toshiharu Suzuki
  The EMBO journal, 26, 6, 1475, 86, 21 Mar. 2007, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• SYD-2 Liprin-alpha organizes presynaptic active zone formation through ELKS.
  Ya Dai; Hidenori Taru; Scott L Deken; Brock Grill; Brian Ackley; Michael L Nonet; Yishi Jin
  Nature neuroscience, 9, 12, 1479, 87, Dec. 2006, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Suppression of the caspase cleavage of beta-amyloid precursor protein by its cytoplasmic phosphorylation.
  Hidenori Taru; Kazuaki Yoshikawa; Toshiharu Suzuki
  FEBS letters, 567, 2-3, 248, 52, 04 Jun. 2004, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein.
  Hidenori Taru; Toshiharu Suzuki
  The Journal of biological chemistry, 279, 20, 21628, 36, 14 May 2004, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Differential roles of JIP scaffold proteins in the modulation of amyloid precursor protein metabolism.
  Hidenori Taru; Yutaka Kirino; Toshiharu Suzuki
  The Journal of biological chemistry, 277, 30, 27567, 74, 26 Jul. 2002, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Expression and characterization of the Drosophila X11-like/Mint protein during neural development.
  Momoko Hase; Yoshimasa Yagi; Hidenori Taru; Susumu Tomita; Akio Sumioka; Kazuya Hori; Kanako Miyamoto; Takeshi Sasamura; Makoto Nakamura; Kenji Matsuno; Toshiharu Suzuki
  Journal of neurochemistry, 81, 6, 1223, 32, Jun. 2002, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Interaction of Alzheimer's beta -amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade.
  Hidenori Taru; Ko-Ichi Iijima; Momoko Hase; Yutaka Kirino; Yoshimasa Yagi; Toshiharu Suzuki
  The Journal of biological chemistry, 277, 22, 20070, 8, 31 May 2002, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein
  Susumu Tomita; Toshinori Ozaki; Hidenori Taru; Shinobu Oguchi; Shizu Takeda; Yoshimasa Yagi; Shigeru Sakiyama; Yutaka Kirino; Toshiharu Suzuki
  Journal of Biological Chemistry, 274, 4, 2243, 2254, 22 Jan. 1999, [Peer-reviewed], [International Magazine]
  English, Scientific journal

• Role of synaptic transmission in the signaling pathway of regulating aging in C. elegans
  中川健斗; 鈴木利治; 鈴木利治; 前仲勝実; 多留偉功, 日本薬学会年会要旨集(Web), 145th, 2025
• Role of synaptic transmission in lifespan regulation through neuropeptide secretion in C. elegans
  中川健斗; 鈴木利治; 多留偉功, 日本薬学会年会要旨集(Web), 144th, 2024
• Complementary effects of SYD-2/Liprin-α on lifespan regulation through neuropeptide secretion in C. elegans
  中川健斗; 石川智規; 鈴木利治; 多留偉功, 日本薬学会年会要旨集(Web), 143rd, 2023
• Analysis of the interaction between DLK, a regulator of axonal development, and kinesin-1 motor
  宮沢桃子; 中島愛弓; 鈴木利治; 多留偉功, 日本薬学会年会要旨集(Web), 143rd, 2023
• RIMB-1/RIM-Binding Protein and UNC-10/RIM Redundantly Regulate Presynaptic Localization of the Voltage-Gated Calcium Channel in Caenorhabditis elegans.
  Yuto Kushibiki; Toshiharu Suzuki; Yishi Jin; Hidenori Taru, The Journal of neuroscience : the official journal of the Society for Neuroscience, 140年会, 44, 28L, am08S, Mar. 2020, [International Magazine]
  Presynaptic active zones (AZs) contain many molecules essential for neurotransmitter release and are assembled in a highly organized manner. A network of adaptor proteins known as cytomatrix at the AZ (CAZ) is important for shaping the structural characteristics of AZ. Rab3-interacting molecule (RIM)-binding protein (RBP) family are binding partners of the CAZ protein RIM and also bind the voltage-gated calcium channels (VGCCs) in mice and flies. Here, we investigated the physiological roles of RIMB-1, the homolog of RBPs in the nematode Caenorhabditis elegans RIMB-1 is expressed broadly in neurons and predominantly localized at presynaptic sites. Loss-of-function animals of rimb-1 displayed slight defects in motility and response to pharmacological inhibition of synaptic transmission, suggesting a modest involvement of rimb-1 in synapse function. We analyzed genetic interactions of rimb-1 by testing candidate genes and by an unbiased forward genetic screen for rimb-1 enhancer. Both analyses identified the RIM homolog UNC-10 that acts together with RIMB-1 to regulate presynaptic localization of the P/Q-type VGCC UNC-2/Cav2. We also find that the precise localization of RIMB-1 to presynaptic sites requires presynaptic UNC-2/Cav2. RIMB-1 has multiple FN3 and SH3 domains. Our transgenic rescue analysis with RIMB-1 deletion constructs revealed a functional requirement of a C-terminal SH3 in regulating UNC-2/Cav2 localization. Together, these findings suggest a redundant role of RIMB-1/RBP and UNC-10/RIM to regulate the abundance of UNC-2/Cav2 at the presynaptic AZ in C. elegans, depending on the bidirectional interplay between CAZ adaptor and channel proteins.SIGNIFICANCE STATEMENT Presynaptic active zones (AZs) are highly organized structures for synaptic transmission with characteristic networks of adaptor proteins called cytomatrix at the AZ (CAZ). In this study, we characterized a CAZ protein RIMB-1, named for RIM-binding protein (RBP), in the nematode Caenorhabditis elegans Through systematic analyses of genetic interactions and an unbiased genetic enhancer screen of rimb-1, we revealed a redundant role of two CAZ proteins RIMB-1/RBP and UNC-10/RIM in regulating presynaptic localization of UNC-2/Cav2, a voltage-gated calcium channel (VGCC) critical for proper neurotransmitter release. Additionally, the precise localization of RIMB-1/RBP requires presynaptic UNC-2/Cav2. These findings provide new mechanistic insight about how the interplay among multiple CAZ adaptor proteins and VGCC contributes to the organization of presynaptic AZ., (公社)日本薬学会, Japanese
• 神経機能発現機構の最前線: 神経単位の遺伝子発現制御とタンパク質の階層的かつ冗長的機能を探る 神経プレシナプス形成における階層的かつ冗長的なアダプター分子群の制御機能
  多留 偉功, 日本生化学会大会プログラム・講演要旨集, 92回, [1S17a, 02], Sep. 2019
  (公社)日本生化学会, Japanese
• APPファミリー分子のキネシン1による軸索輸送(Axonal transport of APP family cargos by kinesin-1)
  劉 思佳; 加藤 俊; 奥村 佑香; 多留 偉功; 鈴木 利治, 日本生化学会大会プログラム・講演要旨集, 92回, [1T17m, 04], Sep. 2019
  (公社)日本生化学会, English
• 神経機能発現機構の最前線: 神経単位の遺伝子発現制御とタンパク質の階層的かつ冗長的機能を探る 神経プレシナプス形成における階層的かつ冗長的なアダプター分子群の制御機能
  多留 偉功, 日本生化学会大会プログラム・講演要旨集, 92回, [1S17a, 02], Sep. 2019
  (公社)日本生化学会, Japanese
• APPファミリー分子のキネシン1による軸索輸送(Axonal transport of APP family cargos by kinesin-1)
  劉 思佳; 加藤 俊; 奥村 佑香; 多留 偉功; 鈴木 利治, 日本生化学会大会プログラム・講演要旨集, 92回, [1T17m, 04], Sep. 2019
  (公社)日本生化学会, English
• APPとAlcadeinαの神経細胞における機能解析
  李 姓陳; 白木 柚葉; 多留 偉功; 羽田 沙緒里; 鈴木 利治, Dementia Japan, 32, 3, 433, 433, Sep. 2018
  (一社)日本認知症学会, Japanese
• 線虫C.elegans神経プレシナプスアダプター分子RIMB-1による電位依存性カルシウムチャネルの局在制御
  櫛引 勇人; 鈴木 利治; 多留 偉功, 生命科学系学会合同年次大会, 2017年度, [1P, 1274], Dec. 2017
  生命科学系学会合同年次大会運営事務局, Japanese
• 線虫C.elegansにおける神経プレシナプスアダプター分子RIMB-1による電位依存性カルシウムチャネルの局在制御
  櫛引勇人; 鈴木利治; 多留偉功, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 16th, 2017
• 線虫C.elegansアダプター分子RIMB-1による電位依存性カルシウムチャネルの神経プレシナプス局在制御
  櫛引勇人; 鈴木利治; 多留偉功, 日本遺伝学会大会プログラム・予稿集, 89th, 2017
• Regulated axonal transport of APP and alcadein by kinesin-1
  Toshiharu Suzuki; Kyoko Chiba; Yuka Okumura; Yuzuha Shiraki; Yuriko Sobu; Masataka Kinjo; Saori Hata; Hidenori Taru, FASEB JOURNAL, 28, 1, Apr. 2014
  English, Summary international conference
• Identification of a cell adhesion molecule involved in negative regulation of presynaptic assembly in C. elegans
  Hidenori Taru, FASEB JOURNAL, 27, Apr. 2013
  English, Summary international conference
• アルツハイマー病関連分子の新規な細胞内輸送制御機構の解析
  多留 偉功, 医科学応用研究財団研究報告, 29, 156, 159, Feb. 2012
  (公財)鈴木謙三記念医科学応用研究財団, Japanese
• 線虫DDニューロンのプレシナプス除去に関わる遺伝子の探索
  星野裕子; 多留偉功; 多留偉功, 日本生化学会大会(Web), 85th, 2012
• Essential Role of a Conserved Homophilic Interaction Domain of SYD-2/Liprin-alpha Protein in Presynaptic Assembly in C. elegans.
  H. Taru, MOLECULAR BIOLOGY OF THE CELL, 22, 2011
  English, Summary international conference
• APP輸送において働く分子 JIP1bとKLCの結合機構の詳細
  千葉 杏子; 野澤 啓輔; 内藤 志保; 多留 偉功; 鈴木 利治, Dementia Japan, 24, 3, 402, 402, Sep. 2010
  (一社)日本認知症学会, Japanese
• Regulatory Interaction of SYD-1 in the specification of presynaptic sites in C.elegans
  多留偉功; JIN Yishi, 生化学, 2010
• APP軸索輸送機構におけるKLCとJIPの結合制御機構
  野澤 啓輔; 内藤 志保; 多留 偉功; 鈴木 利治, Dementia Japan, 23, 2, 200, 200, Aug. 2009
  (一社)日本認知症学会, Japanese
• 神経系の新しい細胞内情報伝達様式 創薬の新規標的としての可能性をさぐる プレシナプス部位の決定に関わる情報伝達系 SYD-1とアダプター分子群の相互作用
  多留 偉功; Jin Yishi, 日本薬学会年会要旨集, 127年会, 1, 187, 187, Mar. 2007
  (公社)日本薬学会, Japanese
• X11Lとアミロイド前駆体タンパク質APPの結合制御機構の解析
  田中絵美; 佐久間めぐみ; 多留偉功; 中矢正; 鈴木利治, 日本分子生物学会年会講演要旨集, 28th, 2005
• Stress-induced phosphorylation of beta-amyloid precursor protein by JNK and its facilitation by XII-like/MINT2 protein
  H Taru; T Suzuki, NEUROBIOLOGY OF AGING, 25, S161, S161, Jul. 2004
  English, Summary international conference
• JNK‐interacting proteins and amyloid precursor protein
  多留偉功; 鈴木利治, 生体の科学, 55, 2, 133, 138, Apr. 2004
  (公財)金原一郎記念医学医療振興財団, Japanese
• 神経変性疾患 その原因探索と創薬への道 Aβ産生を制御するAPP代謝調節因子群の作用機構と創薬ターゲットの開発
  鈴木 利治; 荒木 陽一; 吉田 知弘; 宮城 尚美; 住岡 暁夫; 多留 偉功; 中矢 正, 日本薬学会年会要旨集, 124年会, 1, 224, 224, Mar. 2004
  (公社)日本薬学会, Japanese
• Alcadein結合タンパク質AlcBPによるAβ産生抑制機構の解析
  吉田知弘; 荒木陽一; 住岡暁夫; 多留偉功; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 26th, 2003
• アルツハイマーアミロイド前駆体タンパク質ファミリーのJNKによるリン酸化とその制御
  多留偉功; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 26th, 2003
• Amyloid precursor-like protein 2(APLP2)のリン酸化の解析
  鹿島理沙; 多留偉功; 中矢正; 川口映子; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 26th, 2003
• 神経変性機構解明への生化学的アプローチ アルツハイマーアミロイド前駆体タンパク質の結合タンパク質による代謝及びリン酸化制御
  多留 偉功; 鈴木 利治, 生化学, 74, 8, 656, 656, Aug. 2002
  (公社)日本生化学会, Japanese
• Characterization of X11-like binding protein, XB51
  A Sumioka; H Taru; S Tomita; T Suzuki, NEUROBIOLOGY OF AGING, 23, 1, S195, S195, Jul. 2002
  English, Summary international conference
• Evolutionally conserved interactions of amyloid precursor protein family members implicated in the metabolims
  H Taru; K Iijima; M Hase; Y Yagi; T Suzuki, NEUROBIOLOGY OF AGING, 23, 1, S188, S188, Jul. 2002
  English, Summary international conference
• モチーフ・ドメインリスト 遺伝子発現/転写および関連事象 Relホモロジードメイン
  多留偉功; 馳桃子; 鈴木利治, 生体の科学, 52, 5, 386, 387, Oct. 2001
  (公財)金原一郎記念医学医療振興財団, Japanese
• Identification and characterization of a novel evolutionary conserved interaction of beta-amyloid precursor protein family
  H Taru; Y Yagi; M Hase; S Tomita; Y Kirino; T Suzuki, FASEB JOURNAL, 15, 5, A1167, A1167, Mar. 2001
  English, Summary international conference
• APP細胞質ドメインおよびX11-likeを中心とした細胞内Protein Interaction Mappingの解析
  鈴木利治; 富田進; LEE D-S; 安藤香奈絵; 飯島浩一; 多留偉功; 高畠愛子; 馳桃子; 武田志津, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 2000
• 神経発生と神経変性における分子基盤 アルツハイマー病関連因子の神経発生における機能
  武田 志津; 安藤 香奈絵; 富田 進; 飯島 浩一; 馳 桃子; 多留 偉功; 八木 克将; 桐野 豊; 糸原 重美; 鈴木 利治, 生化学, 71, 8, 639, 639, Aug. 1999
  (公社)日本生化学会, Japanese
• ヒトAPP結合タンパク質hX11Lのショウジョウバエホモログ遺伝子(dX11L)の単離と機能解析
  馳桃子; 八木克将; 多留偉功; 富田進; 桐野豊; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 1999
• 新規ショウジョウバエAPPL結合タンパク質の解析とほ乳類相同分子の単離
  多留偉功; 八木克将; 富田進; 馳桃子; 桐野豊; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 1999
• Isolation and Characterization of Drosophila APPL Binding Proteins
  TARU H.; YAGI Y.; TOMITA S.; HASE M.; KIRINO Y.; SUZUKI T., 日本分子生物学会年会プログラム・講演要旨集, 21, 656, 656, 01 Dec. 1998
  Japanese
• Isolation and Characterization of Drosophila homologue of human XIIL
  HASE Momoko; YAGI Yoshimasa; TOMITA Susumu; TARU Hidenori; KIRINO Yutaka; SUZUKI Toshiharu, 日本分子生物学会年会プログラム・講演要旨集, 21, 657, 657, 01 Dec. 1998
  Japanese
• APP結合タンパク質X11Lのショウジョウバエホモログ遺伝子の単離と解析
  馳桃子; 八木克将; 富田進; 多留偉功; 桐野豊; 鈴木利治, 日本分子生物学会年会プログラム・講演要旨集, 21st, 1998
• Screening of Procerebral Lobe Specific Protein in Land Slug.
  多留偉功; 中矢正; 川原茂敬; 鈴木利治; 桐野豊, 日本分子生物学会年会プログラム・講演要旨集, 20th, 1997

• タンパク質がわかる
  多留偉功; 中矢正; 鈴木利治, タンパク質の構造変化・代謝異常と神経変性疾患
  羊土社, 2003, [Contributor]

• 生命科学研究, 2024年, 修士課程, 生命科学院
• 生命薬学特論, 2024年, 修士課程, 生命科学院
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• 先端生物科学実験法Ⅱ, 2024年, 学士課程, 薬学部
• 生命科学論文講読Ⅰ, 2024年, 修士課程, 生命科学院
• 生理学, 2024年, 学士課程, 薬学部
• 生命科学論文講読Ⅱ, 2024年, 修士課程, 生命科学院
• 細胞生物学Ⅱ, 2024年, 学士課程, 薬学部
• 基礎実習, 2024年, 学士課程, 薬学部
• 分析化学実習, 2024年, 学士課程, 薬学部
• 物理化学実習, 2024年, 学士課程, 薬学部

• THE JAPANESE BIOCHEMICAL SOCIETY
• THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
• THE PHARMACEUTICAL SOCIETY OF JAPAN
• American Society for Biochemistry and Molecular Biology
• Society for Neuroscience

• Regulatory mechanism of neuronal presynaptic elimination by adaptor molecules and cytoskeletons
  Grants-in-Aid for Scientific Research
  01 Apr. 2023 - 31 Mar. 2026
  多留 偉功
  脳神経系の情報処理機能は、神経細胞間のシナプスと呼ばれる接着構造が適切に形成・維持され、また時に除去されることで実現されている。神経伝達物質の放出を担うプレシナプス（シナプス前部）構造の除去が発生過程あるいは加齢に伴ってどのように制御されているかについては不明な点が多く、その分子機構の理解は神経科学の重要な課題である。代表者らはモデル動物である線虫C. elegansにおいて、微小管の不安定化に起因したプレシナプス異常に関与する二つのアダプター分子を同定した。本研究は神経プレシナプス除去において、これらMAGUKファミリー分子およびLIMドメイン分子がはたす役割とその作用分子機構を明らかにすることを目的とする。さまざまなシナプス異常変異体との遺伝学的相互作用を検討した結果、これらのアダプター分子は微小管不安定化に伴うプレシナプスの除去に対して選択的に関わることが示唆された。アダプター分子の結合分子から予想されるアクチン線維制御との関わりについて遺伝学的に検討し、アダプター分子の作用が当初想定されたアクチン制御とは一部異なる経路による可能性を明らかにした。さらに遺伝子導入による解析から、MAGUKファミリー分子は主に下皮で発現するものの、神経細胞における機能がプレシナプス除去に関わる可能性が示された。シナプス形成・維持・除去の異常は種々の精神疾患・神経疾患に密接に関与しており、本研究はそれらの発症機序を分子レベルで理解する基盤として、治療法開発への貢献が期待される。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 23K06128
• Molecular mechanisms regulating the localization of presynaptic voltage-gated calcium channels
  Grants-in-Aid for Scientific Research
  01 Apr. 2020 - 31 Mar. 2023
  Taru Hidenori
  The nervous system processes information through communication between neurons at synapses. The precise localization of the voltage-gated calcium channel Cav2 as a trigger molecule at presynaptic sites is essential for synaptic transmission. In this study, using the nematode C. elegans as a model organism, we explored molecules involved in the localization of Cav2 through genetic analysis. We newly revealed that the functions of enzymes involved in neuropeptide maturation and glycosylation regulation are important for Cav2 localization at presynaptic sites.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 20K07046
• Regulation of neuronal adaptor molecules by voltage-gated calcium channels at presynaptic structures
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2016 - 31 Mar. 2020
  Taru Hidenori
  In neuronal presynaptic sites, neurotransmitter release is triggered by voltage-gated calcium channels (VGCC) and supported by unique basal structures with a group of adaptor proteins. In this study, we analyzed the molecular mechanism of protein localization to presynaptic sites focusing on the relationship between VGCC and the adapter molecule RIMB-1/RIM-BP in C. elegans, an invertebrate model animal. We revealed that the localization of VGCC is mainly regulated by the redundant function of two adaptor molecules, RIMB-1 and UNC-10. Moreover, we identified the requirement of VGCC and endocytic proteins for the localization of RIMB-1.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 16K08223
• Molecular mechanisms of presynaptic assembly in serotonergic neurons HSN in C. elegans
  Grants-in-Aid for Scientific Research
  Apr. 2013 - Mar. 2017
  TARU Hidenori
  At presynaptic structures in neurons, Cytomatrix at the Active Zone (CAZ)”, a group of unique adapter proteins, assembles and organizes functional molecules specialized for synaptic transmission. This project addressed the molecular mechanisms of presynaptic assembly mainly in serotonergic neurons HSN in nematode C. elegans: SYD-1, a key regulator of presynaptic assembly, negatively regulates GTPase through the binding of RhoGAP-like domain; RIMB-1, previously uncharacterized CAZ protein, regulates the localization of voltage-gated calcium channels at presynaptic structures.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 25460058
• Roles of SYD-1 and SYD-2 proteins and neuronal trafficking in presynaptic formation
  Grants-in-Aid for Scientific Research
  Apr. 2011 - Mar. 2013
  TARU Hidenori
  Neuronal synapses are cell adhesion structures, which are fundamental units for functions of neuronal system. In nematode C.elegans, SYD (SYnapse Defective) -1 and SYD-2 have been identified as central regulators of presynaptic formation. Based on a large scale modifier screen and genetic analysis, we proposed a possibility that presynaptic components are precisely assembled by SYD-1/SYD-2 pathway under negative regulation involving a cadherin-like cell-adhesion molecule.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 23790070
• Regulatory mechanisms of presynaptic assembly by an adaptor protein SYD-2
  Grants-in-Aid for Scientific Research
  Apr. 2009 - Mar. 2011
  TARU Hidenori
  Neuronal synapses are critical cell adhesion structures, which are specialized for intercellular signal transduction between neurons. To understand the molecular mechanisms of synaptic formation is one of the important challenges in neuroscience field and provides better understanding of higher brain function such as learning and memory and neurodegenerative diseases. An adapter protein SYD-2 is a key molecule for presynaptic assembly in nematode C.elegans. In this study, we showed that oligomerization is a critical step for the activation of SYD-2, and identified multiple modifier mutants, which may work together with SYD-2 for presynaptic assembly.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 21790057

• βアミロイド生成抑制剤
  Patent right, 鈴木 利治; 多留 偉功; 佐久間 めぐみ; 田中 絵美; 中矢 正, 国立大学法人 北海道大学
  特願2005-139114, 11 May 2005
  特開2006-315982, 24 Nov. 2006
  200903077351557646