2013 Fiscal Year Final Research Report
Study on the molecular mechanisms underlying CAPS-mediated exocytosis of dense-core vesicles containing BDNF and catecholamine
| Project/Area Number |
23300137
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | CAPS1 / CAPS2 / 有芯小胞 / BDNF / トランスゴルジ網 / 自閉症 |
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| Research Abstract |
We showed that CAPS1 and CAPS2 interacts with Arf4/5, which is possibly involved in dense-core vesicle (DCV) trafficking in the trans-Golgi network (TGN). Dex3 (deletion of exon3) is a rare alternative splicing CAPS2 variant which was identified to be increased in some of patients with autism. We generated a dex3-expressing mice and verified an impairment in axonal dex3 localization, contributing to a reduction in BDNF release from axons and thereby resulting in abnormal synapses. Dex3 mice also showed deficits in social and anxiety behaviors, suggesting a possible association of dex3 with brain development and behavior related to autism. Although CAPS1 regulates insulin secretion, its function in the brain is essentially unknown because of neonatal death of CAPS1 KO mice. We generated CAPS1 conditional knockout mice and suggested that loss of CAPS1 disrupts the TGN-DCV pathway and BDNF release, which may be associated with a mechanism underlying diabetes and comorbid depression.
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[Journal Article] CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain2013
Author(s)
Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-SembaR, Sekine Y, Sato Y, Tanaka M, Iwasato T, Itohara S, Furuyama K, Kawaguchi Y, Ishizaki Y, Yuzaki M and Furuichi T
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Journal Title
J. Neurosci
Volume: 33
Pages: 17326-17334
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[Journal Article] Astrocytic Ca^<2+> signals are required for the functional integrity of tripartite synapses2013
Author(s)
Tanaka, M., Shih, PY., Gomi, H., Yoshida, H., Nakai, J., Ando, R., Furuichi, T., Mikoshiba, K., Semyanov, A., and Itohara, S
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Journal Title
Mol. Brain
Volume: 6
Pages: 6
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[Journal Article] Mouse models of mutations and variations in autism spectrum disorder-associated genes : mice expressing caps2/cadps2 copy number and alternative splicing variants2013
Author(s)
Sadakata, T., Shinoda, Y., Sato, A., Iguchi, H., Ishii, C., Matsuo, M., Yamaga, R., Furuichi, T
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Journal Title
Int J Environ Res Public Health
Volume: 10(12)
Pages: 6335-6353
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[Journal Article] Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice2012
Author(s)
Sadakata, T., Shinoda, Y., Oka, M., Sekine, Y., Sato, Y., Saruta, C., Miwa, H., Tanaka, M., Itohara, S., and Furuichi, T
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Journal Title
Proc. Natl. Acad. Sci. U.S.A
Volume: 109
Pages: 21104-21109
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[Journal Article] PLD4 is involved in phagocytosis of microglia : expression and localization changes of PLD4 are correlated with activation state of micrglia2011
Author(s)
Otani, Y., Yamaguchi, Y., Sato, Y., Furuichi, T., Ikenaka, K., Kitani, H., and Baba, H
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Journal Title
PLoS One
Volume: 6(11)
Pages: e27544
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[Journal Article] Phase advance of the light-dark cycle perturbs diurnal rhythms of brain-derived neurotrophic factor and neurotrophin-3 protein levels, which reduces synaptophysin-positive presynaptic terminals in the cortex of juvenile rats2011
Author(s)
Hamatake, M., Miyazaki, N., Sudo, K., Matsuda, M., Sadakata, T., Furuya, A., Ichisaka, S., Hata, Y., Nakagawa, C., Nagata, K., Furuichi, T., Katoh-Semba, R
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 21478-21487
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[Journal Article] Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network2011
Author(s)
Shinoda, Y., Sadakata, T., Nakao, K., Katoh-Semba, R., Kinameri, E., Furuya, A., Yanagawa, Y., Hirase, H., and Furuichi, T
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Journal Title
Proc. Natl. Acad. Sci. U.S.A
Volume: 108
Pages: 373-378
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[Journal Article] Systematizing and cloning of genes involved in the cerebellar cortex circuit development2011
Author(s)
Furuichi, T., Shiraishi-Yamaguchi, Y., Sato, A., Sadakata, T., Huang, J., Shinoda, Y., Hayashi, K., Mishima, Y., Tomomura, M., Nishibe, H., and Yoshikawa, F
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Journal Title
Neurochem Res
Volume: 36
Pages: 1241-1252
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