Spatio-temporal regulation of cellular trafficking and signal transduction

• Project/Area Number: 21247031
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Nagoya University
• Principal Investigator: MATSUMOTO Kunihiro 名古屋大学, 理学研究科, 教授 (70116375)
• Co-Investigator(Kenkyū-buntansha): HISAMOTO Naoki 名古屋大学, 大学院・理学研究科, 准教授 (80283456) ; HANAHUSA Hiroshi 名古屋大学, 大学院・理学研究科, 助教 (00345844)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000); Fiscal Year 2011: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2010: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: シグナル伝達 / 細胞内トラフィック / プロテインキナーゼ / モーター蛋白質 / LRRK1 / EGFR / endosome / endocytosis / EGF受容 / エンドサイトーシス / ダイニンモータ / ESCRT-0 / MVB sortin / EGF受容体 / MVB sorting

Research Abstract

(1) Neurons are polarized cells that contain distinct sets of proteins in their axons and dendrites. Synaptic vesicles(SV) and many SV proteins are exclusively localized in the presynaptic regions but not in dendrites. We found that a MAPKKK-like kinase LRK-1 acts in the same pathway as UNC-16 and is required for the formation of proper volume of transport vesicles from Golgi apparatus.
(2) Activation of the epidermal growth factor receptor(EGFR) triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. These events are important for the regulation of mitogenic EGFR signaling. We revealed that leucine-rich repeat kinase 1(LRRK1), a member of ROCO kinase family, forms a complex with activated EGFR through an interaction with Grb2 and is involved in the trafficking of EGFR from early to late endosomes. We showed that EGFR negatively regulates the kinase activity of LRRK1 by Tyr-944 phosphorylation and that this is required for proper endosomal trafficking of EGFR.

Research Products

• [Journal Article] The growth factor SVH-1 regulates axon regeneration in C.elegans via the JNK MAPK cascade (2012)
  • Author(s): Chun Li
  • Journal Title: Nature Neuroscience Volume: 15 Issue: 4 Pages: 551-557
  • DOI: 10.1038/nn.3052
  • Peer Reviewed
• [Journal Article] NLK positively regulates Wnt/β-catenin signaling by phosphorylating LEF1 in neural progenitor cells (2012)
  • Author(s): Ota, S., Ishitani, S., Shimizu, N., Matsumoto, K., Itoh, M., and Ishitani. T
  • Journal Title: EMBO J Volume: 31 Issue: 8 Pages: 1904-1915
  • DOI: 10.1038/emboj.2012.46
  • Peer Reviewed
• [Journal Article] Epithelial TAK1 kinase is activated through two independent mechanisms and regulates reactive oxygen species (2012)
  • Author(s): Omori, E. Inagaki, M., Mishina, Y., Matsumoto, K., and Ninomiya-Tsuji, J
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Issue: 9 Pages: 3365-3370
  • DOI: 10.1073/pnas.1116188109
  • Peer Reviewed
• [Journal Article] EGFR-dependent phosphorylation of leucine-rich repeat kinase LRRK1 is important for proper endosomal trafficking of EGFR (2012)
  • Author(s): Kouki Ishikawa, Atsuki Nara, Kunihiro Matsumoto, Hiroshi Hanafusa
  • Journal Title: Molecular Biology of the Cell Volume: 7 Issue: 7 Pages: 1294-1306
  • DOI: 10.1091/mbc.e11-09-0780
  • Peer Reviewed
• [Journal Article] Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor (2011)
  • Author(s): Hanafusa, H., Ishikawa, K., Kedashiro, S., Saigo, K., Iemura, S., 4 Natsume, T., Komada, M., Shibuya, H., Nara, A., and Matsumoto, K
  • Journal Title: Nature Commun Volume: 2 Issue: 1 Pages: 158-158
  • DOI: 10.1038/ncomms1161
  • Peer Reviewed
• [Journal Article] A shift of the TOR adaptor from rictor toward raptor by semaphorin in C. elegans (2011)
  • Author(s): Nukazuka, A., Tamaki, S., Matsumoto, K., Oda, Y., Fujisawa, H., and Takagi, S
  • Journal Title: Nature Commun Volume: 2 Issue: 1 Pages: 484-484
  • DOI: 10.1038/ncomms1495
  • Peer Reviewed
• [Journal Article] Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways (2011)
  • Author(s): Nix, P., Hisamoto, H., Matsumoto, K., and Bastiani, M
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 26 Pages: 10738-10743
  • DOI: 10.1073/pnas.1104830108
  • Peer Reviewed
• [Journal Article] The C. elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein (2011)
  • Author(s): Arimoto, M., Koushika, S. P., Choudhary, B. C., Li, C., Matsumoto, K., and Hisamoto, N
  • Journal Title: J. Neurosci Volume: 31 Issue: 6 Pages: 2216-2224
  • DOI: 10.1523/jneurosci.2653-10.2011
  • Peer Reviewed
• [Journal Article] Non-canonicalβ-catenin degradation mediates reactive oxygen speciesinduced epidermal cell death (2011)
  • Author(s): Omori, E., Matsumoto, K., and Ninomiya-Tsuji, J
  • Journal Title: Oncogene Volume: 30 Issue: 30 Pages: 3336-3344
  • DOI: 10.1038/onc.2011.49
  • Peer Reviewed
• [Journal Article] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization (2011)
  • Author(s): Ishitani, S., Inaba, K., Matsumoto, K., and Ishitani, T
  • Journal Title: Mol. Biol. Cell Volume: 22 Issue: 2 Pages: 266-277
  • DOI: 10.1091/mbc.e10-07-0605
  • NAID: 120004979399
  • Peer Reviewed
• [Journal Article] Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans (2011)
  • Author(s): Yuan, Y., Cao, P., Smith, M. A., Kramp, K., Huang, Y., Hisamoto, N., Matsumoto, K., Hatzoglou, M., Jin, H., and Feng, Z
  • Journal Title: PLoS One Volume: 6 Issue: 8 Pages: e22354-e22354
  • DOI: 10.1371/journal.pone.0022354
  • Peer Reviewed
• [Journal Article] Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins (2011)
  • Author(s): Hayakawa, T., Kato, K., Hayakawa, R., Hisamoto, N., Matsumoto, K., Takeda, K. and Ichijo, H.
  • Journal Title: Genetics Volume: 187 Issue: 3 Pages: 785-792
  • DOI: 10.1534/genetics.110.124883
  • Peer Reviewed
• [Journal Article] TGF-β-activated kinase 1 mediates mechanical stress-induced IL-6 expression in osteoblasts (2011)
  • Author(s): Fukuno, N., Matsui, H., Kanda, Y., Suzuki, O., Matsumoto, K., Sasaki, K., Kobayashi, T., and Tamura, S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 408 Pages: 202-207
  • URL: http://dx.doi.org/10.1016/j.bbrc.2011.02.127
  • Peer Reviewed
• [Journal Article] Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor. (2011)
  • Author(s): Hanafusa, H., Ishikawa, K., Kedashiro, S., Saigo, K., lemura, S., Natsume, T., Komada, M., Shibuya, H., Nara, A., Matsumoto, K.
  • Journal Title: Nature Commun. Volume: 2 Pages: 158-158
  • Peer Reviewed
• [Journal Article] Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex (2010)
  • Author(s): Ishitani, T., Hirao, T., Suzuki, M., Isoda, M., Ishitani, S., Harigaya, K., Kitagawa, M., Matsumoto, K., and Itoh, M
  • Journal Title: Nature Cell Biol Volume: 12 Issue: 3 Pages: 278-285
  • DOI: 10.1038/ncb2028
  • NAID: 120005293254
  • Peer Reviewed
• [Journal Article] Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans (2010)
  • Author(s): Shivers, R. P., Pagano, D. J., Kooistra1, T., Richardson, C. E., Reddy, K. C., Whitney, J. K., Matsumoto, K., Hisamoto, N., and Kim, D. H
  • Journal Title: PLoS Genet Volume: 6 Issue: 4 Pages: e1000892-e1000892
  • DOI: 10.1371/journal.pgen.1000892
  • Peer Reviewed
• [Journal Article] Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells (2010)
  • Author(s): Omori, E., Matsumoto, K., Zhu, S., Smart, R. C., and Ninomiya-Tsuji, J
  • Journal Title: Cancer Res Volume: 70 Issue: 21 Pages: 8417-8425
  • DOI: 10.1158/0008-5472.can-10-1227
  • Peer Reviewed
• [Journal Article] Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions (2010)
  • Author(s): Yamamoto, M., Morita, R., Mizoguchi, T., Matsuo, H., Isoda, M., Ishitani, T., Chitnis, A. B., Matsumoto, K., Crump, J. G., Hozumi, K., Yonemura, S., Kawakami, K., and Itoh, M
  • Journal Title: Development Volume: 137 Issue: 15 Pages: 2527-2537
  • DOI: 10.1242/dev.051011
  • Peer Reviewed
• [Journal Article] The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the JNK signaling pathway mediating the stress response (2010)
  • Author(s): Fujiki, K., Mizuno, T., Hisamoto, N., and Matsumoto, K
  • Journal Title: Mol. Cell. Biol Volume: 30 Issue: 4 Pages: 995-1003
  • DOI: 10.1128/mcb.01131-09
  • Peer Reviewed
• [Journal Article] TAK1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium (2010)
  • Author(s): Kajino-Sakamoto, R., Omori, E., Nighot, P. K., Blikslager, A. T., Matsumoto, K., and Ninomiya-Tsuji, J
  • Journal Title: J. Immunol Volume: 185 Issue: 8 Pages: 4729-4737
  • DOI: 10.4049/jimmunol.0903587
  • Peer Reviewed
• [Journal Article] A TAK1 kinase adaptor, TAB2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in TNF signaling pathway (2010)
  • Author(s): Broglie, P., Matsumoto, K., Akira, S., Brautigan, D. L., and Ninomiya-Tsuji, J
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 4 Pages: 2333-2339
  • DOI: 10.1074/jbc.m109.090522
  • Peer Reviewed
• [Journal Article] The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans (2010)
  • Author(s): Okuyama, T., Inoue, H., Ookuma, S., Satoh, T., Kano, K., Honjoh, S., Hisamoto, N., Matsumoto, K. and Nishida, E.
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 39 Pages: 30274-30281
  • DOI: 10.1074/jbc.m110.146274
  • Peer Reviewed
• [Journal Article] Delta1 family members are involved in filopodial actin formation and neuronal cell migration independent of Notch signaling (2010)
  • Author(s): Sugiyama, K., Nishide, K., Matsuo, H., Okigawa, S., Okano, M., Ishitani, T., Matsumoto, K., and Itoh, M
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 398 Pages: 118-124
  • URL: http://dx.doi.org/10.1016/j.bbrc.2010.06.047
  • Peer Reviewed
• [Journal Article] Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex. (2010)
  • Author(s): Ishitani, T., Hirao, T., Suzuki, M., Isoda, M., Ishitani, S., Harigaya, K., Kitagawa, M., Matsumoto, K, Itoh, M.
  • Journal Title: Nature Cell Biol. Volume: 12 Pages: 278-285
  • NAID: 120005293254
  • Peer Reviewed
• [Journal Article] Phosphorylation of the Conserved Transcription Factor ATF-7 by PMK-1 p38 MAPK Regulates Innate Immunity in Caenorhabditis elegans. (2010)
  • Author(s): Shivers, R.P., Pagano, D.J., Kooistra, T., Richardson, C.E., Reddy, K.C., Whitney, J.K., Matsumoto, K., Hisamoto, N., Kim, D.H.
  • Journal Title: PloS Genet. Volume: 6
  • Peer Reviewed
• [Journal Article] Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active (2010)
  • Author(s): Ishitani, T., Hirao, T., Suzuki, M., Isoda, M., Ishitani, S., Harigaya, K., Kitagawa, M., Matsumoto, K., Itoh, M.
  • Journal Title: Nature Cell Biol. 12 Pages: 278-285
  • Peer Reviewed
• [Journal Article] Regulation of the ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • Author(s): Hanafusa, H., Matsumoto, K., and Nishida, E
  • Journal Title: Nature Cell Biol Volume: 11 Issue: 1 Pages: 106-109
  • DOI: 10.1038/ncb1820
  • Peer Reviewed
• [Journal Article] LRRK2 modulates vulnerability to mitochondrial dysfunction in C. elegans (2009)
  • Author(s): Saha, S., Guillily, M., Ferree, A., Lanceta, J., Chan, D., Ghosh, J., Hsu, C., Segal, L., Raghavan, K., Matsumoto, K., Hisamoto, N., Kuwahara, T., Iwatsubo, T., Moore, L., Goldstein, L., Cookson, M., and Wolozin, B
  • Journal Title: J. Neurosci Volume: 29 Issue: 29 Pages: 9210-9218
  • DOI: 10.1523/jneurosci.2281-09.2009
  • Peer Reviewed
• [Journal Article] TAK1 kinase determines TRAIL sensitivity by modulating reactive oxygen species and cIAP (2009)
  • Author(s): Morioka1, S., Omori, E., Kajino, T., Kajino-Sakamoto, R., Matsumoto, K., and Ninomiya-Tsuji, J
  • Journal Title: Oncogene Volume: 28 Issue: 23 Pages: 2257-2265
  • DOI: 10.1038/onc.2009.110
  • Peer Reviewed
• [Journal Article] C. elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation (2009)
  • Author(s): Hiatt, S. M., Duren, H. M., Shyu, Y. J., Ellis, R. E., Hisamoto, N., Matsumoto, K., Kariya, K., Kerppola, T. M., and Hu, C-D
  • Journal Title: Mol. Biol. Cell Volume: 20 Issue: 17 Pages: 3888-3895
  • DOI: 10.1091/mbc.e08-08-0833
  • Peer Reviewed
• [Journal Article] Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin (2009)
  • Author(s): Ishitani, T., Ishitani, S., Matsumoto, K., and Itoh, M
  • Journal Title: J. Neurochem Volume: 111 Issue: 5 Pages: 1104-1118
  • DOI: 10.1111/j.1471-4159.2009.06400.x
  • Peer Reviewed
• [Journal Article] A mechanism for the suppression of IL-1-induced NF-κB activation by the protein phosphatase 2Cε-2 (2009)
  • Author(s): Henmi, T., Amano, K., Nagaura, Y., Matsumoto, K., Echigo, S., Tamura, S., and Kobayashi, T
  • Journal Title: Biochem. J Volume: 423 Issue: 1 Pages: 71-78
  • DOI: 10.1042/bj20090208
  • Peer Reviewed
• [Journal Article] The Germinal Center Kinase GCK-1 is a negative regulator of MAP kinase activation and apoptosis in the C. elegans germline (2009)
  • Author(s): Schouest, K. R., Kurasawa, Y., Furuta, T., Hisamoto, N., Matsumoto, K., and Schumacher, J. M
  • Journal Title: PLoS One Volume: 4 Issue: 10 Pages: e7450-e7450
  • DOI: 10.1371/journal.pone.0007450
  • Peer Reviewed
• [Journal Article] Regulation of the ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • Author(s): Hanafusa, H., Matsumoto, K., Nishida, E.
  • Journal Title: Nature Cell Biol. 11 Pages: 106-109
  • Peer Reviewed
• [Journal Article] C. elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation (2009)
  • Author(s): Hiatt, S.M., Duren, H.M., Shyu, Y.J., Ellis, R.E., Hisamoto, N., Matsumoto, K., Kariya, K., Kerppola, T.M., Hu, C-D.
  • Journal Title: Mol.Biol.Cell 20 Pages: 3888-3895
  • Peer Reviewed
• [Presentation] WNK-1 negatively regulates formation of diacylglycerol in C. elegans (2011)
  • Author(s): 福薗嵩,久本直毅,松本邦弘
  • Organizer: 18th International C. elegans Meeting
  • Place of Presentation: アメリカUniversity of California
• [Presentation] LRRK1 regulates endosomal trafficking of EGFR transport by phosphorylating CLIP-170 (2011)
  • Author(s): 慶田城迅,高島成二,花房洋,松本邦弘
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学学術交流館
• [Presentation] 線虫新規増殖因子SVH-1とその受容体チロシンキナーゼSVH-2はJNK型MAPK経路を介して神経軸索再生を制御する (2011)
  • Author(s): 李春,久本直毅, Nix Paola,金尾朱夏,水野智亮, Bastiani Michael,松本邦弘
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 線虫をモデル動物とした神経再生を誘導する因子/受容体の解析 (2010)
  • Author(s): 李春、水野智亮、久本直毅、松本邦弘
  • 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: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] ROCOファミリーキナーゼLRRK1によるEGFR細胞内トラフィック制御 (2009)
  • Author(s): 花房洋, 松本邦弘
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Remarks]
  • URL: http://bunshi3.bio.nagoya-u.ac.jp/~bunshi6/matsumoto_new/index.html