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NAKASHIMA AkioBiosignal Research CenterAssociate Professor
Research activity information
■ Paper- Diacylglycerol kinase β (DGKβ) is an enzyme that converts diacylglycerol to phosphatidic acid and is mainly expressed in the cerebral cortex, hippocampus and striatum. We previously reported that DGKβ induces neurite outgrowth and spinogenesis, contributing to higher brain functions, including emotion and memory. To elucidate the mechanisms involved in neuronal development by DGKβ, we investigated the importance of DGKβ activity in the induction of neurite outgrowth using human neuroblastoma SH-SY5Y cells. Interestingly, both wild-type DGKβ and the kinase-negative (KN) mutant partially induced neurite outgrowth, and these functions shared a common pathway via the activation of mammalian target of rapamycin complex 1 (mTORC1). In addition, we found that DGKβ interacted with the small GTPase RalA and that siRNA against RalA and phospholipase D (PLD) inhibitor treatments abolished DGKβKN-induced neurite outgrowth. These results indicate that binding of RalA and activation of PLD and mTORC1 are involved in DGKβKN-induced neurite outgrowth. Taken together with our previous reports, mTORC1 is a key molecule in both kinase-dependent and kinase-independent pathways of DGKβ-mediated neurite outgrowth, which is important for higher brain functions.Dec. 2021, Biomolecules, 11(12) (12), English, International magazine[Refereed]Scientific journal
- Meiosis is a specialized cell division process that mediates genetic information transfer to the next generation. Meiotic chromosomal segregation occurs when DNA replication is completed during the pre-meiotic S phase. Here, we show that Schizosaccharomyces pombe Pef1, an orthologue of mammalian cyclin-dependent kinase 5 (CDK5), is required to promote pre-meiotic DNA replication. We examined the efficiency of meiotic initiation using pat1-114 mutants and found that, meiotic nuclear divisions did not occur in the pef1Δ pat1-114 strain. Deletion of pef1 also suppressed the expression of DNA replication factors and the phosphorylation of Cdc2 Tyr-15. The double deletion of clg1 and psl1 arrested meiotic initiation in pat1-114 mutant cells, similar to that of pef1-deficient cells. Meiotic progression was also slightly delayed in the pas1-deficient strain. Our results reveal that Pef1 regulates cyclin-coordinated meiotic progression.Corresponding, Jan. 2021, Biomolecules, 11(1) (1), English, International magazine[Refereed]Scientific journal
- Although senescent cells display various morphological changes including vacuole formation, it is still unclear how these processes are regulated. We have recently identified the gene, lymphocyte antigen 6 complex, locus D (LY6D), to be upregulated specifically in senescent cells. LY6D is a glycosylphosphatidylinositol-anchored cell-surface protein whose function remains unknown. Here, we analyzed the functional relationship between LY6D and the senescence processes. We found that overexpression of LY6D induced vacuole formation and knockdown of LY6D suppressed the senescence-associated vacuole formation. The LY6D-induced vacuoles were derived from macropinocytosis, a distinct form of endocytosis. Furthermore, Src family kinases and Ras were found to be recruited to membrane lipid rafts in an LY6D-dependent manner, and inhibition of their activity impaired the LY6D-induced macropinocytosis. Finally, reduction of senescent-cell survival induced by glutamine deprivation was recovered by albumin supplementation to the culture media in an LY6D-dependent manner. Because macropinocytosis acts as an amino acid supply route, these results suggest that LY6D-mediated macropinocytosis contributes to senescent-cell survival through the incorporation of extracellular nutrients.Nov. 2020, The Journal of biological chemistry, 296, 100049 - 100049, English, International magazine[Refereed]Scientific journal
- In Schizosaccharomyces pombe, a general strategy for survival in response to environmental changes is sexual differentiation, which is triggered by TORC1 inactivation. However, mechanisms of TORC1 regulation in fission yeast remain poorly understood. In this study, we found that Pef1, which is an ortholog of mammalian CDK5, regulates the initiation of sexual differentiation through positive regulation of TORC1 activity. Conversely, deletion of pef1 leads to activation of autophagy and subsequent excessive TORC1 reactivation during the early phases of the nitrogen starvation response. This excessive TORC1 reactivation results in the silencing of the Ste11-Mei2 pathway and mating defects. Additionally, we found that pef1 genetically interacts with tsc1 and tsc2 for TORC1 regulation, and physically interacts with three cyclins, Clg1, Pas1 and Psl1. The double deletion of clg1 and pas1 promotes activation of autophagy and TORC1 during nitrogen starvation, similar to what is seen in pef1Δ cells. Overall, our work suggests that Pef1-Clg1 and Pef1-Pas1 complexes regulate initiation of sexual differentiation through control of the TSC-TORC1 pathway and autophagy.Corresponding, Sep. 2020, Journal of cell science, 133(17) (17), English, International magazine[Refereed]Scientific journal
- Diacylglycerol kinase β (DGKβ) is an enzyme converting DG to phosphatidic acid (PA) and is specifically expressed in neurons, especially those in the cerebral cortex, hippocampus and striatum. We previously reported that DGKβ induces neurite outgrowth and spinogenesis, contributing to higher brain function including emotion and memory, and plasma membrane localization of DGKβ via the C1 domain and a cluster of basic amino acids at the C-terminus is necessary for its function. To clarify the mechanisms involved in neuronal development by DGKβ, we investigated whether DGKβ activity induces neurite outgrowth using human neuroblastoma SH-SY5Y cells. DGKβ induced neurite outgrowth by activation of mammalian target of rapamycin complex 1 (mTORC1) through a kinase-dependent pathway. In addition, in primary cultured cortical and hippocampal neurons, inhibition of mTORC1 abolished DGKβ induced-neurite outgrowth, branching and spinogenesis. These results indicated that DGKβ induces neurite outgrowth and spinogenesis by activating mTORC1 in a kinase-dependent pathway.Mar. 2020, Neurochemistry international, 134, 104645 - 104645, English, International magazine[Refereed]Scientific journal
- Misfolded and aggregated proteins are eliminated to maintain protein homeostasis. Autophagy contributes to the removal of protein aggregates. However, if and how proteotoxic stress induces autophagy is poorly understood. Here we show that proteotoxic stress after treatment with azetidine-2-carboxylic acid (AZC), a toxic proline analog, induces autophagy in budding yeast. AZC treatment attenuated target of rapamycin complex 1 (TORC1) activity, resulting in the dephosphorylation of Atg13, a key factor of autophagy. By contrast, AZC treatment did not affect target of rapamycin complex 2 (TORC2). Proteotoxic stress also induced TORC1 inactivation and autophagy in fission yeast and human cells. This study suggested that TORC1 is a conserved key factor to cope with proteotoxic stress in eukaryotic cells.Apr. 2019, Biochemical and biophysical research communications, 511(2) (2), 434 - 439, English, International magazineScientific journal
- Jan. 2019, Life Science Alliance, 2(1) (1), e201800045, EnglishD-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species[Refereed]Scientific journal
- Apr. 2017, JOURNAL OF CELL SCIENCE, 130(8) (8), 1413 - 1420, English[Refereed]Scientific journal
- Oct. 2016, NUCLEIC ACIDS RESEARCH, 44(18) (18), 8704 - 8713, English[Refereed]Scientific journal
- Aug. 2016, SCIENTIFIC REPORTS, 6, English[Refereed]Scientific journal
- May 2016, PLOS ONE, 11(5) (5), English[Refereed]Scientific journal
- Jan. 2016, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 469(3) (3), 377 - 383, English[Refereed]Scientific journal
- Jul. 2015, JOURNAL OF BIOMEDICAL SCIENCE, 22(1) (1), English[Refereed]Scientific journal
- Jun. 2014, BIOLOGY OPEN, 3(6) (6), 542 - 552, English[Refereed]Scientific journal
- Apr. 2014, PLOS ONE, 9(4) (4), English[Refereed]Scientific journal
- Nov. 2013, PLOS ONE, 8(11) (11), English[Refereed]Scientific journal
- Lead, Sep. 2013, FEBS LETTERS, 587(18) (18), 2924 - 2929, English[Refereed]Scientific journal
- Aug. 2013, CELL CYCLE, 12(16) (16), 2617 - 2624, English[Refereed]Scientific journal
- Lead, Apr. 2013, JOURNAL OF BIOMEDICAL SCIENCE, 20(1) (1), English[Refereed]Scientific journal
- Lead, Dec. 2012, JOURNAL OF CELL SCIENCE, 125(23) (23), 5840 - 5849, English[Refereed]Scientific journal
- Jun. 2012, FEBS LETTERS, 586(11) (11), 1612 - 1616, English[Refereed]Scientific journal
- May 2012, CELL DEATH & DISEASE, 3(5) (5), English[Refereed]Scientific journal
- Jun. 2010, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(25) (25), 11234 - 11239, English[Refereed]Scientific journal
- May 2010, ONCOGENE, 29(18) (18), 2746 - 2752, EnglishScientific journal
- Mar. 2010, JOURNAL OF CELL SCIENCE, 123(5) (5), 777 - 786, EnglishScientific journal
- 1, Jan. 2010, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 55(1) (1), 11 - 17, Japanese[Rheb-mTOR signaling pathway involved in tumor formation].[Refereed]
- May 2009, JOURNAL OF BIOLOGICAL CHEMISTRY, 284(19) (19), 12783 - 12791, EnglishScientific journal
- May 2008, PLOS ONE, 3(5) (5), English[Refereed]Scientific journal
- Feb. 2008, JOURNAL OF BIOLOGICAL CHEMISTRY, 283(7) (7), 4430 - 4438, EnglishScientific journal
- Sep. 2007, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 361(1) (1), 218 - 223, English, International magazine[Refereed]Scientific journal
- Jul. 2007, JOURNAL OF BIOLOGICAL CHEMISTRY, 282(28) (28), 20329 - 20339, EnglishScientific journal
- Jun. 2006, CURRENT GENETICS, 49(6) (6), 403 - 413, English[Refereed]Scientific journal
- Jan. 2006, JOURNAL OF BIOCHEMISTRY, 139(1) (1), 129 - 135, EnglishScientific journal
- Oct. 2002, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 66(10) (10), 2224 - 2227, English[Refereed]Scientific journal
- Mar. 2002, JOURNAL OF BIOCHEMISTRY, 131(3) (3), 391 - 398, EnglishGenes for a nuclease and a protease are involved in the drastic decrease in cellular RNA amount in fission yeast cells during nitrogen starvation[Refereed]Scientific journal
- May 2001, CURRENT GENETICS, 39(3) (3), 166 - 174, English[Refereed]Scientific journal
- MDPI AG, 01 Sep. 2017, Biomolecules, 7(3) (3), e50, English[Refereed][Invited]Book review
- 2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 100P - 100P, EnglishmTOR is involved in both kinase activity-dependent and -independent pathways of DGK beta-regulated neurite and branch inductionSummary international conference
- Sep. 2012, FEBS JOURNAL, 279, 383 - 384, EnglishInvolvement of mTOR in diacylglycerol kinase beta (DGK beta)-induced neurite blanching and spine formationSummary international conference
- 羊土社, 2011, 実験医学, 29, 865 - 870, Japaneseアミノ酸センシングシステムとしてのmTOR複合体1の機序[Invited]Introduction commerce magazine
- ELSEVIER, 2010, Enzymes, 28(C) (C), 167 - 187, English[Invited]Others
- 共立出版, Jan. 2010, 蛋白質 核酸 酵素, 55(1) (1), 11 - 17, JapaneseRheb-mTORシグナルと細胞がん化への関与[Invited]Introduction commerce magazine
- 医学書院, 2008, 生体と科学, 59(6) (6), 497 - 503, Japanese[Invited]Introduction commerce magazine
- 北隆館, 2004, BIO Clinica, 19, 18 - 22, Japanese細胞環境中のアミノ酸バランスを感知するmTORシグナル伝達機構[Invited]Introduction commerce magazine
- 01 Dec. 1998, 日本分子生物学会年会プログラム・講演要旨集, 21, 581 - 581, JapaneseFunction of a fission yeast RNA/DNA degrading enzyme in nitrogen starvation response
- Joint work, Conservation of the Tsc/Rheb/TORC1/S6K/S6 signaling in fission yeast, 2010The Enzymes
- Joint work, 共立出版, Jan. 2010, JapaneseRheb-mTORシグナルと細胞がん化への関与/蛋白質 核酸 酵素Scholarly book
- Joint work, 北陸館, 2004, JapaneseBIO Clinica Vol. 19 / 細胞環境中のアミノ酸バランスを感知するmTORシグナル伝達機構Scholarly book
- 第46回日本分子生物学会年会, Japanese減数分裂過程におけるオートファジーの制御機構及び生理的役割Poster presentation
- 第13回TOR研究会, Japanese分裂酵母の減数分裂におけるTORC1とオートファジーの制御Oral presentation
- 第56回酵母遺伝学フォーラム, Japanese分裂酵母TORC1の減数分裂過程における制御機構Poster presentation
- 第56回酵母遺伝学フォーラム, Japanese分裂酵母の減数分裂におけるオートファジー制御Poster presentation
- 第45回日本分子生物学会年会, Dec. 2022, Japanese分裂酵母おける減数分裂進行に伴うオートファジーの発生と役割についてPoster presentation
- 第12回TOR研究会, Oct. 2022, Japanese分裂酵母の減数分裂におけるTORC1活性とオートファジーOral presentation
- 第44回日本分子生物学会年会,パシフィコ横浜, Dec. 2021, JapaneseRegulation of autophagy during meiosis in Schizosaccharomyces pombePoster presentation
- 第11回TOR研究会, Jul. 2021, Japanese分裂酵⺟の減数分裂におけるTORC1活性とオートファジーOral presentation
- 第42回日本分子生物学会年会, Dec. 2019, Japanese分裂酵母サイクリン依存性キナーゼPef1はTORC1を介して減数分裂の開始・進行を制御するPoster presentation
- 酵母遺伝学フォーラム第52回研究報告,静岡市清水文化会館マリナート, Sep. 2019, Japanese分裂酵母Pef1/TORC1シグナル伝達機構の解析Oral presentation
- 第9回TOR研究会, Jun. 2019, Japanese, 久留米シティプラザ 久留米市, Domestic conference分裂酵母Pef1/CDK5によるTORC1制御機構Oral presentation
- 第41回日本分子生物学会年会, Nov. 2018, Japanese, 横浜市,パシフィコ横浜, Domestic conference有性生殖過程における分裂酵母Pef1(CDK5)/TORC1シグナル伝達機構の解析Poster presentation
- 第41回日本分子生物学会年会, Nov. 2018, Japanese, Domestic conferenceLY6Dは老化細胞の細胞膜脂質ラフト上でSrcやRasと会合することによりマクロピノサイトーシスを誘導するPoster presentation
- 酵母遺伝学フォーラム第51回研究報告会, Sep. 2018, Japanese, 福岡市,九州大学医学部百年講堂, Domestic conference分裂酵母Pef1/CDK5はTORC1を介して有性生殖過程の開始・進行を制御するPoster presentation
- 第8回TOR研究会, Jun. 2018, Japanese, 蛋白研セミナー“TORを介した細胞成長統御の総合的理解”, 大阪市,大阪大学中之島センター, Domestic conference分裂酵母Pef1/CDK5はTORC1制御に関与する?Oral presentation
- ConBio2017(生命科学系学会合同年次大会), Dec. 2017, Japanese, 神戸ポートアイランド, Domestic conference減数分裂における分裂酵母TORC1の制御[Invited]Invited oral presentation
- ConBio2017, Dec. 2017, Japanese, 神戸, Domestic conferenceLY6Dにより誘導されるマクロピノサイトーシスは老化細胞の生存促進に働くOral presentation
- 第四回バイオシグナル研究会「栄養シグナリングTOR と細胞機能制御〜基礎研究から創薬へ〜」, Sep. 2017, Japanese, 神戸大学瀧川記念学術交流会館, Domestic conferenceモデル生物を用いたTORC1 の減数分裂における制御と機能[Invited]Invited oral presentation
- 日本分子生物学会, Nov. 2016, Japanese, 横浜, Domestic conferencep53によるアミノ酸代謝経路の調節が細胞老化を誘導するPublic symposium
- 第6回TOR研究会, Sep. 2016, Japanese, 東京大学 分子細胞生物学研究所, Domestic conferenceフェロモン応答シグナルによる分裂酵母TORC1制御の可能性Oral presentation
- Biochemistry and Molecular Biology 2015, Dec. 2015, Japanese, 特定非営利活動法人 日本分子生物学会, 神戸ポートアイランド, Domestic conferenceRegulation and function of TORC1 signaling in meiosis under nitrogen starvation[Invited]Invited oral presentation
- THE EIGHTH INTERNATIONAL FISSION YEAST MEETING, Jun. 2015, English, Kobe, International conferenceRegulation of TORC1 signaling in meiosis under nitrogen starvationPoster presentation
- 第37回日本分子生物学会, Nov. 2014, Japanese, 横浜, Domestic conference新規細胞老化誘導因子としてのDアミノ酸酸化酵素DAOの機能解析Poster presentation
- 第37回日本分子生物学会年会, Nov. 2014, Japanese, パシフィコ横浜, Domestic conferenceプロリン脱水素酵素(PRODH)は細胞老化誘導に関わる新規因子であるPoster presentation
- 第47回酵母遺伝学フォーラム報告会, Sep. 2014, Japanese, 東京大学農学部弥生キャンパス東京大学弥生講堂, Domestic conference分裂酵母 TORC1 の窒素源飢餓時の再活性化と生理機能Poster presentation
- 第186回酵母細胞研究会例会 平成24年度地神芳文記念研究助成金研究成果報告会, Jul. 2014, Japanese, Domestic conference多機能性 TORC1 キナーゼの液胞依存性栄養シグナルによる活性制御システムの解明[Invited]Invited oral presentation
- 第36回日本分子生物学会年会, Dec. 2013, Japanese, 日本分子生物学会, Domestic conference栄養枯渇時の分裂酵母TORC1の活性と機能Oral presentation
- 第46回酵母遺伝学フォーラム年会, Sep. 2013, Japanese, 酵母遺伝学フォーラム, Domestic conference分裂酵母TORC1の窒素源飢餓時の再活性化と生理機能の検討Oral presentation
- 第35回日本分子生物学会年会, Dec. 2012, Japanese, 日本分子生物学会, Domestic conference分裂酵母アレスチン様タンパク質Arn1とそのユビキチン化を介したアミノ酸の細胞内取り込みの制御Poster presentation
- 第45回酵母遺伝学フォーラム年会, Sep. 2012, Japanese, 酵母遺伝学フォーラム, Domestic conferenceアミノ酸トランスポーターCat1のアレスチン様タンパク質による機能制御Poster presentation
- The 35th Annual Meeting of the Japan Neuroscience Society, Sep. 2012, Japanese, Japan Neuroscience Society, Nagoya Congress Center, Domestic conferenceMolecular mechanism of DGKβ- mediated neurite blanching and spine formationPoster presentation
- The 22nd IUBMB & the 37th FEBS, Sep. 2012, English, IUBMB & FEBS, Sevilla, Spain, International conferenceInvolvement of mTOR in Diacylglycerol kinase β (DGKβ)-induced neurite branching and spine formation.Poster presentation
- 第54回日本脂質生化学会大会, Jun. 2012, Japanese, 日本脂質生化学会, 九州大学, Domestic conferenceジアシルグリセロールキナーゼ_による特徴的な神経突起伸にはmTORが関与するOral presentation
- 第34回日本分子生物学会年会, Dec. 2011, English, 日本分子生物学会, Domestic conferenceMammalian TIP41-like protein, mTIP41, as a positive regulator of the amino acid-stimulated mTORC1 signaling.Oral presentation
- 第44回酵母遺伝学フォーラム年会, Sep. 2011, Japanese, 酵母遺伝学フォーラム, Domestic conferenceアレスチン様タンパク質Art1によるアミノ酸透過酵素Cat1の機能解析Poster presentation
- BMB2010(日本生化学会・日本分子生物学会合同大会), Dec. 2010, Japanese, 日本分子生物学会, Domestic conference分裂酵母TORC1によるS6キナーゼPsk1の制御Oral presentation
- 第43回酵母遺伝学フォーラム年会, Sep. 2010, Japanese, 酵母遺伝学フォーラム, Domestic conference分裂酵母TORC1による栄養依存的なリボソームタンパクS6のリン酸化制御Oral presentation
- The 5th international fission yeast meeting, 2009, English, International conferenceTHE TORC1-S6K-S6 SIGNALING IN FISSION YEAST.Poster presentation
■ Research Themes
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2022 - 31 Mar. 2025Establishment and spread of the new assay for sperm flagellar function to improve artificial insemination results in the cattle
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2022 - 31 Mar. 2025減数分裂におけるTORC1キナーゼおよびオートファジーの機能制御の分子機構
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Challenging Research (Exploratory), Challenging Research (Exploratory), Kobe University, 28 Jun. 2019 - 31 Mar. 2021Analyses of 3-dimensional rotation for the purpose of reconsidering criteria for the evaluation of flagellar functions in bull sperm
- 学術研究助成基金助成金/基盤研究(C), Apr. 2016 - Mar. 2019Competitive research funding
- 学術研究助成基金助成金/基盤研究(C), Apr. 2014 - Mar. 2017, Principal investigatorCompetitive research funding
- 科学研究費補助金/若手研究(B), Apr. 2011 - Mar. 2013, Principal investigatorCompetitive research funding
- 科学研究費補助金/基盤研究(B), 2010Competitive research funding
- 分裂酵母のストレス適応機構の研究.Competitive research funding
- ストレス適応の分子メカニズムの研究Competitive research funding
- TORを介する栄養シグナリングの解明と細胞制御機構の解析Competitive research funding
- Research on the molecular mechanism of the stress-response.Competitive research funding
- Study of the stress-response mechanism in fission yeast.Competitive research funding