Study on the regulatory mechanism of the CAPS protein-mediated trafficking pathway of dense-core vesicles

• Project/Area Number: 26290026
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Science
• Principal Investigator: FURUICHI TEIICHI 東京理科大学, 理工学部, 教授 (50219094)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 有芯小胞 / CAPSタンパク質 / シナプス小胞 / 発達障害 / 開口放出 / 神経科学 / シナプス / 社会行動 / BDNF / コルチコステロン

Outline of Final Research Achievements

1) We showed that expression of a rare alternative splicing subtype lacking exon3 causes impairments in development of cerebellar neurons as well as synaptic transmission at parallel fiber-Purkinje cell synapses. 2) We suggested that CAPS2 is involved in stress hormone response and insulin secretion in response to chronic stress. 3) We suggest that the interaction of CAPS1 with a small GTPase septin regulates the trafficking of secretory vesicles. 4) We showed that CAPS1 regulates stability of releasable synaptic vesicles at the active zone of hippocampal CA3-CA1 synapses.

Research Products

• [Journal Article] The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination (2017)
  • Author(s): Hayashi K, Furuya A, Sakamaki Y, Akagi T, Shinoda Y, Sadakata T, Hashikawa T, Shimizu K, Minami H, Sano Y, Nakayama M, and Furuichi T.
  • Journal Title: PLoS ONE Volume: 12 Issue: 3 Pages: e0173175-e0173175
  • DOI: 10.1371/journal.pone.0173175
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Analysis of gene expression in Ca2+-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways (2016)
  • Author(s): Sadakata T, Shinoda Y, Ishizaki Y, Furuichi T.
  • Journal Title: Neuroscience Letters Volume: 639 Pages: 88-93
  • DOI: 10.1016/j.neulet.2016.12.068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mammalian-specific central myelin protein Opalin is redundant for normal myelination: structural and behavioral assessments (2016)
  • Author(s): Yoshikawa, F., Sato, Y., Tohyama, K., Akagi, T., Furuse, T., Sadakata, T., Tanaka, M., Shinoda, Y., Hashikawa, T., Itohara, S., Sano, Y., Ghandour, SM., Wakana, S., and Furuichi, T.
  • Journal Title: PLoS ONE Volume: 11 Issue: 11 Pages: e0166732-e0166732
  • DOI: 10.1371/journal.pone.0166732
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Galacto-N-biose is neuroprotective against glutamate-induced excitotoxicity in vitro. (2016)
  • Author(s): Shinoda, Y., Nakajima, Y., Iguchi, H., Tatsumi, S., Kitaoka, M., Nakajima, M., Takahashi, T., Fujiwara, M., and Furuichi, T.
  • Journal Title: Eur. J. Pharmacol. Volume: 791 Pages: 711-717
  • DOI: 10.1016/j.ejphar.2016.10.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus (2016)
  • Author(s): 6.Shinoda Y, Ishii C, Fukazawa Y, Sadakata T, Ishii Y, Sano Y, Iwasato T, Itohara S, Furuichi T
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31540-31540
  • DOI: 10.1038/srep31540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity (2016)
  • Author(s): Nakajima Y, Iguchi H, Kamisuki S, Sugawara F, Furuichi T and Shinoda Y
  • Journal Title: The Journal of Toxicological Sciences Volume: 41 Issue: 2 Pages: 311-319
  • DOI: 10.2131/jts.41.311
  • NAID: 130005132670
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Interaction of Ca2+-dependent activator protein for secretion 1 (CAPS1) with septin family proteins in mouse brain (2016)
  • Author(s): Hosono M, Shinoda Y, Hirano T, Ishizaki Y, Furuichi T and Sadakata T
  • Journal Title: Neurosci. Lett. Volume: 617 Pages: 232-235
  • DOI: 10.1016/j.neulet.2016.02.035
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice. (2015)
  • Author(s): Yuriko Mishima, Yo Shinoda, Tetsushi Sadakata, Masami Kojima, Shigeharu Wakana, Teiichi Furuichi.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 1-6
  • DOI: 10.1038/srep08932
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum. (2014)
  • Author(s): Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Saruta C, Ishizaki Y, Yuzaki M, Kojima M, Furuichi T.
  • Journal Title: PLoS One. Volume: 9(6) Issue: 6 Pages: 1-10
  • DOI: 10.1371/journal.pone.0099524
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Age-dependent redistribution and hypersialylation of the central myelin paranodal loop membrane protein Opalin in the mouse brain. (2014)
  • Author(s): Yumi Sato, Fumio Yoshikawa, Tetsushi Sadakata, Yo Shinoda, Michinori Koebis, Teiichi Furuichi.
  • Journal Title: Neurosci Letter Volume: 581 Pages: 14-19
  • DOI: 10.1016/j.neulet.2014.08.017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain (2014)
  • Author(s): Okamura-Oho Y, Shimokawa K, Nishimura M, Takemoto S, Sato A, Furuichi T, Yokota H.
  • Journal Title: Scientific Report Volume: 4 Issue: 1 Pages: 6969-6969
  • DOI: 10.1038/srep06969
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration. (2014)
  • Author(s): Tanabe et al.
  • Journal Title: PLOS ONE Volume: 9 Issue: 3 Pages: e92291-e92291
  • DOI: 10.1371/journal.pone.0092291
  • Peer Reviewed / Open Access
• [Presentation] A deficiency of Ca2+-dependent activator protein for secretion 1 affects hippocampal long-term potentiation (2016)
  • Author(s): Y. Ishii, C. Ishii, Y. Shinoda, Y. Sano, T. Furuichi
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] A rubber tail task in Ca2+-dependent activator protein for secretion (CAPS2) knockout mice (2016)
  • Author(s): M. Wada, M. Ide, T. Atsumi, K. Yagishita, M., Katakai, Y., Shinoda, T. Furuichi, K.,Kansaku
  • Organizer: Society for Neuroscienc
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Enhancing Brain Transcriptome Database by Neural Gene Ontology (2016)
  • Author(s): T. Furuichi
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 神奈川県横浜市・パシフィコ横浜
  • Year and Date: 2016-07-20
  • Invited
• [Presentation] Databasing brain gene expression information. (2016)
  • Author(s): T. Furuichi
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Nodes Workshop
  • Place of Presentation: RIKEN Suzuki Umetaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research / Invited
• [Presentation] Brain Transcriptome Database (BrainTx) (2016)
  • Author(s): A. Sato, N. Munemura, Y. Sano, Y. Shinoda, T. Sadakata, N. Morita, M. Yuzaki, T. Inoue, M. Hashimoto, H. Ohwada, H. Nishibe, Y. Yamaguchi, T. Furuichi
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Nodes Workshop
  • Place of Presentation: RIKEN Suzuki Umemotaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Parallelization of the registration method for ISH images into the 3D standard brain atlas (2016)
  • Author(s): D. Miyammoto, H. Ikeno, Y. Okamura-Oho, Y. Okamura, N. Munemura, A. Sato, Y. Yamaguchi, R. Kanzaki, T. Furuichi.
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Node Workshop
  • Place of Presentation: RIKEN Suzuki Umemotaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Brain development transcriptome database and developmental disorder. (2015)
  • Author(s): Furuichi, T.
  • Organizer: The 15th China-Japan-Korea Joint Workshop on Neurobiology and Neuroinformatics (NBNI2015)
  • Place of Presentation: Haeundae Centum Hotel, Pusan, Korea
  • Year and Date: 2015-12-20
  • Int'l Joint Research / Invited
• [Presentation] Brain Transcriptome Database (BrainTx, formerly CDT-DB)-Profiling of spatio-temporal gene expression during postnatal development of mouse brain (2015)
  • Author(s): Shinoda, Y., Sato, A., Sadakata, T., Nishibe, H., Morita, N., Inoue, T., Yuzaki, M., Yamaguchi, Y. and Furuichi, T.
  • Organizer: Neuroinformatics 2015
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-20
  • Int'l Joint Research
• [Presentation] The molecular mechanisms of brain development and disorders (2015)
  • Author(s): Furuichi, T.
  • Organizer: INCF Neuroinformatics 2015
  • Place of Presentation: Pullman Cairns International, Cairns, Australia
  • Int'l Joint Research / Invited
• [Presentation] Animal models of autism spectrum disorders:CAPS2 is critical for proper brain development and social behavior (2015)
  • Author(s): Furuichi, T., Shinoda, Y., Sadakata, T.
  • Organizer: International Symposium of the Center for Animal Disease Models 2015
  • Place of Presentation: Gakushi Kaikan, Kanda, Chiyoda-ku, Tokyo
  • Int'l Joint Research / Invited
• [Presentation] Conditional knockout and optogenetic study on the involvement of the secretion-related protein CAPS1 in oxytocin-associated social and maternal behavior (2015)
  • Author(s): Minami, H., Yamaga, R., Shinoda, Y., Sakimura, K., Abe, M., and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] Possible involvement of the secretion-related protein CAPS2 in regulation of endogenous opioid, dynorphin secretion (2015)
  • Author(s): Katakai, M., Shinoda, Y., Christoph, S., and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] Possible involvement of CAPS2 in environmental enrichment-dependent adult neurogenesis in mouse hippocampus (2015)
  • Author(s): Yagishita, K., Shinoda, Y., Senba, R., and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] Expression and function of the mouse RasGEF1 family proteins (2015)
  • Author(s): Hosaka, K., Shinoda, Y. and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice (2015)
  • Author(s): Sadakata, T. and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] CAPS1 associates tethering of SVs on the synaptic plasma membrane (2015)
  • Author(s): Shinoda, Y., Ishii, C., Fukazawa, Y., Sadakata, T., Itohara, S., Iwasato, T., and Furuichi, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県神戸市・神戸コンベンションセンター
• [Presentation] CAPS2-The positive regulation factor of BDNF secretion and the candidate gene for autism (2015)
  • Author(s): Shinoda, Y., Sadakata, T., Hirase, H., and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] Possible involvement of the secretion-related protein CAPS2 in regulation of dynorphin, one of the endogenous opioids, secretion (2015)
  • Author(s): Katakai, M., Shinoda, Y., and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] Function and expression of the mouse RasGEF1 family proteins (2015)
  • Author(s): Hosaka, K., Shinoda, Y. and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] Dual imaging of SVs and DCVs exocytosis (2015)
  • Author(s): Nakajima, Y., Shinoda, Y., and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] Conditional knockout and optogenetic study on the involvement of the secretion-related protein CAPS1 in oxytocin-associated social and maternal behavior. (2015)
  • Author(s): Minami, H., Yamaga, R., Shinoda, Y., Sakimura, K., Abe, M., and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] CAPS1 stabilizes SVs docking state in hippocampal CA3-CA1 synapses (2015)
  • Author(s): Ishii, Y., Ishii, C., Shinoda, Y., Fukazawa, Y., Sadakata, T., Itohara, S., Iwasato, T., and Furuichi, T.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 埼玉県さいたま市・大宮ソニックシティ
• [Presentation] マウス小脳をモデルとした生後期の脳発達と遺伝子発現 (2014)
  • Author(s): 古市貞一
  • Organizer: 第51回 群馬大学脳神経発達統御学セミナー、第9回 ASRLDユニット研究セミナー
  • Place of Presentation: 群馬大学医学部（群馬県前橋市）
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] Age-dependent redistribution and hypersialylation of the central myelin loop membrane protein Opalin in the mouse brain (2014)
  • Author(s): T. FURUICHI, Y. SATO, F. YOSHIKAWA, T. SADAKATA, Y. SHINODA, M. KOEBIS
  • Organizer: Neuroscience 2014, 44th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Walter E. Washington Convention Center (Washington D.C., U.S.A.)
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Tutorial contents on the INCF Japan Node platforms. Neuroscience 2014 (2014)
  • Author(s): Y. YAMAGUCHI, S. SATOH, T. IIJIMA, R. KANZAKI, T. FURUICHI, Y. SHINODA, S. KAKEI, S. MASAKI, H. WAGATSUMA, T. MIYAKAWA, K. TAKAO, H. IKENO, K. TANAKA, Y. OKAMURA-OHO, Y. OKUMURA, S. KAMAKURA, Y. ISONO, Y. MORII, S. SUENAGA, S. USUI.
  • Organizer: 44th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Walter E. Washington Convention Center (Washington D.C., U.S.A.)
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Brain-specific expression of lysosomal-associated membrane protein 5 (LAMP5) gene (2014)
  • Author(s): M. KOEBIS, Y. SAITO, Y. SHINODA, T. FURUICHI
  • Organizer: Neuroscience 2014, 44th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Walter E. Washington Convention Center (Washington D.C., U.S.A.)
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] BDNFの分泌と自閉症 (2014)
  • Author(s): 定方哲史、篠田陽、古市貞一
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会
  • Place of Presentation: 奈良文化会館（奈良県奈良市）
  • Year and Date: 2014-10-01
• [Presentation] 自閉症スペクトラム障害関連の遺伝的な変異や多様性をもった動物モデル (2014)
  • Author(s): 古市貞一
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会
  • Place of Presentation: 奈良文化会館（奈良県奈良市）
  • Year and Date: 2014-09-30
  • Invited
• [Presentation] 成体ニューロン新生におけるCAPS2の役割 (2014)
  • Author(s): 柳下香織、篠田陽、古市貞一
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-13
• [Presentation] 長期増強のシナプス特異性に寄与するプレシナプスタグの探求 (2014)
  • Author(s): 齊藤新平、篠田陽、定方哲史、西岡朋生、貝淵弘三、古市貞一
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-12
• [Presentation] シナプス小胞と有芯小胞における同時イメージング解析 (2014)
  • Author(s): 中島柚依、篠田陽、古市貞一
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-12
• [Presentation] 小脳におけるLAMP5の発現 (2014)
  • Author(s): 古戎道則、齊藤由弦、篠田陽、古市貞一
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11
• [Remarks] Lab of Molecular Neuroscience -Furuichi Lab
  • URL: http://www.lmn.bs.noda.tus.ac.jp/
• [Remarks] 東京理科大学理工学部応用生物科学科古市貞一
  • URL: http://www.tus.ac.jp/fac_grad/p/index.php?64da
• [Remarks] 古市貞一 論文・著書・学会発表
  • URL: http://www.tus.ac.jp/fac_grad/p/achievement.php?64da
• [Remarks] Teiichi Furuichi, Tokyo University of Science
  • URL: http://www.lmn.bs.noda.tus.ac.jp/#!furuichi-info/c1hvv