Searching for substrates of lysosomal cathepsins

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790238
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Juntendo University
• Principal Investigator: KOIKE Masato 順天堂大学, 医学部, 准教授 (80347210)
• Project Period (FY): 2011 – 2012
• Keywords: リソソーム / カテプシン D / ノックアウトマウス / 基質特異性 / ミクログリア / カテプシン C

Research Abstract

For the discovery of substrates for cathepsin D, whole brain lysates from cathepsin D deficient (CD-/-) and the control littermate mice were separated by two-dimensional gel electrophoresis. Several proteins increased in CD-/- mouse brains were identified by mass spectrometry (MS). However immunohistochemical analyses revealed that some of the identified proteins were enriched in active microglia or astrocytes in CD-/- brains. We also found that the protein amount and activity of cathepsin C, whic h is a lysosomal protease and reported to be cleaved by cathepin D in vivo, was increased. However cathepsin C was also detected in activated microglia in CD-/- brains.

Research Products

• [Journal Article] Enrichment of GABARAP relative to LC3 in the axonal initial segments of neurons (2013)
  • Author(s): Koike, M.*, Tanida, I.*, Nanao, T., Tada, N., Iwata, J., Ueno, T., Kominami, E., Uchiyama, Y.
  • Journal Title: PLoS One Volume: 8(5) Pages: e63568
• [Journal Article] ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons (2013)
  • Author(s): Matsui, H.*, Sato, F.*, Sato, S., Koike, M., Taruno, Y., Saiki, S., Funayama, M., Ito, H., Taniguchi, Y., Uemura, N., Toyoda, A., Sakaki, Y., Takeda, S., Uchiyama, Y., Hattori, N., Takahashi, R
  • Journal Title: FEBS letters Volume: 587(9) Pages: 1316-25
• [Journal Article] Biogenesis and proteolytic processing of lysosomal DNase II (2013)
  • Author(s): Ohkouchi, S., Shibata, M., Sasaki, M., Koike, M., Saftig, P., Peters, C., Nagata, S., Uchiyama, Y.
  • Journal Title: PLoS One Volume: 8(3) Pages: e59148
• [Journal Article] Differences in expression patterns of cathepsin C/dipeptidyl peptidase I in normal, pathological and aged mouse central nervous systems. (2013)
  • Author(s): Koike, M., Shibata, M., Ezaki, J., Peters, C., Saftig, P., Kominami, E., Uchiyama, Y.
  • Journal Title: Eur. J. Neurosci. Volume: 37(5) Pages: 816-20
• [Journal Article] Resveratrol affects undifferentiated and differentiated PC12 cells differently, particularly with respect to possible differences in mitochondrial and autophagic functions (2013)
  • Author(s): Hayakawa, N., Shiozaki, M., Shibata, M., Koike, M., Uchiyama, Y., Gotow, T
  • Journal Title: Eur. J. Cell Biol Volume: 92(1) Pages: 30-43
• [Journal Article] c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. (2012)
  • Author(s): Piao, X., Komazawa-Sakon, S., Nishida, T., Koike, M., Piao JH., Ehlken, H., Kurihara, H., Hara, M., van Rooijen, N., Schutz, G., Ohmuraya, M., Uchiyama, Y., Yagita, H., Okumura, K., He YW., Nakano, H.
  • Journal Title: Sci. Signal 5 Volume: 255 Pages: ra93
• [Journal Article] Motor neuron-specific disruption of proteasomes, but not autophagy, replicates amyotrophic lateral sclerosis. (2012)
  • Author(s): Tashiro Y.*, Urushitani, M.*, Inoue, H., Koike, M., Uchiyama, Y., Komatsu, M., Tanaka, K., Yamazaki, M., Abe, M., Misawa, H., Sakimura, K., Ito, H., Takahashi, R
  • Journal Title: J. Biol. Chem. Volume: 109(43) Pages: 42984-94
• [Journal Article] Mitochondrial dysfunction with increased oxidative stress and α-synuclein accumulation inPARK2 iPSC-derived neurons and postmortem brain. (2012)
  • Author(s): Imaizumi, Y., Okada, Y., Akamatsu, W., Koike, M., Kuzumaki, N., Hayakawa, H., Nihira, T., Kobayashi, T., Ohyama, M., Sato, S., Takanashi, M., Funayama, M., Hirayama, A., Soga, T., Hishiki, T., Suematsu, M., Yagi, T., Ito, D., Kosakai, A., Hayashi, K., Shouji, M., Nakanishi, A., Suzuki, N., Mizuno, Y., Mizushima, N., Amagai, M., Uchiyama, Y., Mochizuki, H., Hattori, N., Okano, H.
  • Journal Title: Molecular Brain Volume: 5(1) Pages: 35
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky, D.J. and 1428 authors.
  • Journal Title: Autophagy Volume: 8(4) Pages: 445-544
• [Journal Article] The development of Purkinje cell degeneration in a knockin mouse model reveals lysosomal involvement in the pathogenesis of SCA6 (2012)
  • Author(s): Unno, T., Wakamori, M., Koike, M.,Uchiyama, Y., Ishikawa, K., Kubota, H., Yoshida, T., Sasakawa, H., Peters, C., Mizusawa, H., Watase, K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109(43) Pages: 17693-8
• [Journal Article] Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5 (2012)
  • Author(s): Sekine, S., Kanamaru, Y., Koike, M., Nishihara, A., Okada, M., Kinoshita, H., Kamiyama, M., Maruyama, J., Uchiyama, Y., Ishihara, N., Takeda, K., Ichijo, H.
  • Journal Title: J. Biol. Chem. Volume: 287(41) Pages: 34635-45
• [Journal Article] 神経性セロイドリポフスチン蓄積症における"異常なリソソーム"のオートファジーによる処理 (2012)
  • Author(s): 小池正人、内山安男
  • Journal Title: 生体の科学 Volume: 63(5) Pages: 404-5
• [Journal Article] Grafted human induced pluripotent stem-cell-derived neurospheres promotes motor functional recovery after spinal cord injury in mice (2011)
  • Author(s): Nori, S., Okada, Y., Yasuda, A., Tsuji, O., Takahashi, Y., Kobayashi, Y., Fujiyoshi, K., Koike, M., Uchiyama, Y., Ikeda, E., Toyama, Y., Yamanaka, S., Nakamura, M., Okano, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108(40) Pages: 16825-30
• [Journal Article] Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes (2011)
  • Author(s): Uchida, Y., Hasegawa, J., Chinnapen, D., Inoue, T., Okazaki, S., Kato, R., Wakatsuki, S., Misaki, R., Koike, M., Uchiyama, Y., Iemura, S., Natsume, T., Kuwahara, R., Nakagawa, T., Nishikawa, K., Mukai, K., Miyoshi, E., Taniguchi, N., Sheff, D., Lencer, W.I., Taguchi, T., Arai H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108(38) Pages: 15846-51
• [Journal Article] Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC1 (2011)
  • Author(s): Koyanagi, M., Asahara, S., Matsuda, T., Hashimoto, N., Shigeyama, Y., Shibutani, Y., Kanno, A., Fuchita, M., Mikami, T., Hosooka, T., Inoue, H., Matsumoto, M., Koike, M., Uchiyama, Y., Noda, T., Seino, S., Kasuga, M., Kido, Y
  • Journal Title: PLoS One Volume: 6(8) Pages: e23238
• [Journal Article] Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice (2011)
  • Author(s): Shiozaki, M., Hayakawa, N., Shibata, M., Koike, M., Uchiyama, Y., Gotow, T.
  • Journal Title: Histochem. Cell Biol Volume: 136(4) Pages: 475-89
• [Journal Article] Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease (2011)
  • Author(s): Oguro, M., Koike, M., Ueno, T., Asaoka, D., Mori, H., Nagahara, A., Uchiyama, Y., Watanabe, S.
  • Journal Title: J. Gastroenterol. Volume: 46(5) Pages: 629-38
• [Journal Article] リソソームプロテアーゼの多様性とその病態生理学的役割 (2011)
  • Author(s): 小池正人、内山安男
  • Journal Title: 実験医学増刊号 Volume: 29(12) Pages: 1903-1908
• [Journal Article] Ultrastructural analyses of the rat esophageal stratified epithelium under normal conditions and chronic reflux esophagitis
  • Author(s): Mori, H.*, Koike, M.*, Gotow, T., Ichimura, K., Asaoka, D., Oguro, M., Nagahara, A., Ueno, T., Uchiyama, Y., Watanabe, S
  • Journal Title: Arch. Histol. Cytol Volume: (in press)
• [Book] 「リソソーム内の分解機構」オートファジー 生命をささえる細胞の自己分解システム (水島昇・吉森保編集) (2012)
  • Author(s): 小池正人、内山安男
  • Total Pages: 67-76
  • Publisher: 化学同人
• [Book] 「マウス低酸素-脳虚血負荷後の神経細胞死の遺伝学的検討」ブレインサイエンスレビュー2011 (伊藤正男・川合述史編集) (2011)
  • Author(s): 小池正人
  • Total Pages: 149-168
  • Publisher: クバプロ
• [Remarks]
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/shinkei_kozo/index.html