Screening and analysis of genes involved in regulation of lysosomal dynamics

• Project/Area Number: 22657032
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: KONTANI Kenji 東京大学, 大学院・薬学系研究科, 准教授 (30302615)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,330,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: リソソーム / 膜オルガネラ / 膜輸送 / 線虫 / Gタンパク質 / RNAi / 低分子量G蛋白質 / エンドソーム / オルガネラ / メンブレントラフィック / 小胞輸送

Research Abstract

Lysosomes are membrane organelles responsible for degradation of various macromolecules. Fusion of lysosomes with other membrane organelles is critical for the lysosomal degradation ; however, the molecular mechanism underlying the lysosomal fusion is poorly understood. In the present study, I performed genetic screening for genes involved in regulation of lysosomal dynamics using the nematode C. elegans as a model organism and found that the small GTPase Arl8 may cooperatively function with the HOPS complex to regulate lysosomal fusion.

Research Products

• [Journal Article] RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin (2012)
  • Author(s): Kajiho, H., et al.
  • Journal Title: PLoS One Volume: 7 Issue: 1 Pages: e30575-e30575
  • DOI: 10.1371/journal.pone.0030575
  • Peer Reviewed
• [Journal Article] RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7 (2011)
  • Author(s): Takahashi, S., Ebihara, A., Kajiho, H., Kontani, K., Nishina, H., and Katada, T.
  • Journal Title: Cell Death Differ Volume: 18 Issue: 4 Pages: 645-655
  • DOI: 10.1038/cdd.2010.137
  • Peer Reviewed
• [Journal Article] cTAGE5 mediates collagen secretion through interaction with TANGO1 at endoplasmic reticulum exit sites (2011)
  • Author(s): Saito, K., Yamashiro, K., Ichikawa, Y., Erlmann, P., Kontani, K., Malhotra, V., and Katada, T.
  • Journal Title: Mol Biol Cell Volume: 22 Issue: 13 Pages: 2301-2308
  • DOI: 10.1091/mbc.e11-02-0143
  • Peer Reviewed
• [Journal Article] Characterization of RIN3 as a guanine nucleotide exchange factor for the Rab5 subfamily GTPase Rab31 (2011)
  • Author(s): Kajiho, H., Sakurai, K., Minoda, T., Yoshikawa, M., Nakagawa, S., Fukushima, S., Kontani, K., and Katada, T.
  • Journal Title: J Biol Chem Volume: 286 Issue: 27 Pages: 24364-24373
  • DOI: 10.1074/jbc.m110.172445
  • Peer Reviewed
• [Journal Article] RhoA activation participates in rearrangement of processing bodies and release of nucleated AU-rich mRNAs (2011)
  • Author(s): Takahashi, S., Sakurai, K., Ebihara, A., Kajiho, H., Saito, K., Kontani, K., Nishina, H., and Katada, T.
  • Journal Title: Nucleic Acids Res Volume: 39 Issue: 8 Pages: 3446-3457
  • DOI: 10.1093/nar/gkq1302
  • Peer Reviewed
• [Journal Article] The arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans (2010)
  • Author(s): Nakae I, Fujino T, Kobayashi T, Sasaki A, Kikko Y, Fukuyama M, Gengyo-Ando K, Mitani S, Kontani K, Katada T
  • Journal Title: Mol Biol Cell Volume: 21(14) Issue: 14 Pages: 2434-42
  • DOI: 10.1091/mbc.e09-12-1010
  • Peer Reviewed
• [Journal Article] An Arf-like small G protein, ARL-8, promotes the axonal transport of presynapticcargoes by suppressing vesicle aggregation (2010)
  • Author(s): Klassen MP, Wu YE, Maeder CI, Nakae I, Cueva JG, Lehrman EK, Tada M,Gengyo-Ando K, Wang GJ, Goodman M, Mitani S, Kontani K, Katada T, Shen K
  • Journal Title: Neuron Volume: 66(5) Issue: 5 Pages: 710-23
  • DOI: 10.1016/j.neuron.2010.04.033
  • Peer Reviewed
• [Journal Article] Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans (2010)
  • Author(s): Cevik, S., Hori, Y., Kaplan, O. I., Kida, K., Toivenon, T., Foley-Fisher, C., Cottell, D., Katada, T., Kontani, K., and Blacque, O. E.
  • Journal Title: J Cell Biol Volume: 188 Issue: 6 Pages: 953-969
  • DOI: 10.1083/jcb.200908133
  • Peer Reviewed
• [Journal Article] The arf-like GTPase Ar18 mediates delivery of endocytosed macromoleculesto lysosomes in Caenorhabditis elegans. (2010)
  • Author(s): Nakae I, et al.
  • Journal Title: Mol Biol Cell. Volume: 21 Pages: 2434-2442
  • Peer Reviewed
• [Journal Article] An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation. (2010)
  • Author(s): Klassen MP, et al.
  • Journal Title: Neuron Volume: 66 Pages: 710-723
  • Peer Reviewed
• [Presentation] マルチドメイン型RabファミリーG蛋白質EFCAB4Baの機能解析 (2011)
  • Author(s): 阿部芙美子, 他
  • Organizer: ファーマ・バイオフォーラム2011
  • Place of Presentation: 仙台
  • Year and Date: 2011-10-08
• [Presentation] リソソームへの輸送における低分子量Gタンパク質Arl8の機能解析 (2011)
  • Author(s): 紺谷圏二, 他
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] リソソームへの輸送における低分子量Gタンパク質Ar18の機能解析 (2011)
  • Author(s): 紺谷圏二, 他
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] The ciliary small GTPaseArl13b(I): Arl13b functions at ciliarymembranes and stabilizes intraflagellartransport (2011)
  • Author(s): 堀裕次, 他
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-27
• [Presentation] The ciliary small GTPase Arl13b(II): Arl13b functions at ciliary membranes and stabilizes intraflagellar transport (2011)
  • Author(s): 永島慎一, 他
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-27
• [Presentation] The ciliary small GTPase Arl13b (I) : Arl13b functions at ciliary membranes and stabilizes intraflagellar transport (2011)
  • Author(s): 堀裕次, 他
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-27
• [Presentation] The ciliary small GTPase Arl13b (II) : Arl13b functions at ciliary membranes and stabilizes intraflagellar transport (2011)
  • Author(s): 永島慎一, 他
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-27
• [Presentation] Arf-like GTPaseが介在する細胞内ロジスティクスと関連疾患 (2011)
  • Author(s): 紺谷圏二, 他
  • Organizer: 文部科学省科学研究費補助金新学術領域研究第3回「細胞内ロジスティクス」班会議
  • Place of Presentation: 鳥羽
  • Year and Date: 2011-06-03
• [Presentation] Functional analysis of the ciliary small GTPase Arl13b (2010)
  • Author(s): 堀裕次, 他
  • Organizer: The 3rd Global COE Retreat
  • Place of Presentation: 幕張
  • Year and Date: 2010-12-11
• [Presentation] 線虫C. elegansを用いた低分子量Gタンパク質Ragの機能解析 (2010)
  • Author(s): 壹岐和哉, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 線虫C. elegansを用いたアミノ酸シグナル伝達に介在する低分子量G蛋白質Ragの機能解析 (2010)
  • Author(s): 伊藤有佳子, 他
  • Organizer: ファーマ・バイオフォーラム2010
  • Place of Presentation: 京都
  • Year and Date: 2010-10-02
• [Presentation] 低分子量Gタンパク質Arl13bの繊毛局在化メカニズムの解析 (2010)
  • Author(s): 永島慎一, 他
  • Organizer: ファーマ・バイオフォーラム2010
  • Place of Presentation: 京都
  • Year and Date: 2010-10-02
• [Presentation] A role for C. elegans ARL-8 in endocytic delivery to lysosomes (2010)
  • Author(s): Kontani K, et al.
  • Organizer: FASEB Summer Research Conferences Arf family G protein
  • Place of Presentation: Carefree, Arizona, USA
  • Year and Date: 2010-08-17
• [Presentation] The Arf-like GTPase ARL-8 is required for the removal of apoptotic cells in C.elegans. (2010)
  • Author(s): Sasaki A, et al.
  • Organizer: 4^<th> East Asia C.elegans Meeting
  • Place of Presentation: 東京
  • Year and Date: 2010-07-12
• [Presentation] リソソームの機能制御に介在する低分子量G蛋白質Arl8の解析 (2010)
  • Author(s): 紺谷圏二, 他
  • Organizer: 第9回生命科学研究会
  • Place of Presentation: 筑波
  • Year and Date: 2010-06-25
• [Presentation] リソソームの機能制御に介在する低分子量G蛋白質Ar18の解析 (2010)
  • Author(s): 紺谷圏二, 他
  • Organizer: 第9回生命科学研究会
  • Place of Presentation: 筑波
  • Year and Date: 2010-06-25
• [Presentation] Foxo and RagA link multiple stem cell lineages to coordinate somatic development in C. elegans (2010)
  • Author(s): 福山征光, 他
  • Organizer: 第43回日本発生生物学会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-21
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~seiri
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~seiri/
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~seiri