CAPS1 deficiency perturbs dense-core vesicle trafficking and golgi structure and reduces presynaptic release probability in the mouse brain

Tetsushi Sadakata, Wataru Kakegawa, Yo Shinoda, Mayu Hosono, Ritsuko Katoh-Semba, Yukiko Sekine, Yumi Sato, Mika Tanaka, Takuji Iwasato, Shigeyoshi Itohara, Kenichiro Furuyama, Yoshiya Kawaguchi, Yasuki Ishizaki, Michisuke Yuzaki, Teiichi Furuichi

Research output: Contribution to journalArticle

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Abstract

Ca 2+ -dependent activator protein for secretion 1 (CAPS1) plays a regulatory role in the dense-core vesicle (DCV) exocytosis pathway, but its functions at the cellular and synaptic levels in the brain are essentially unknown because of neonatal death soon after birth in Caps1 knock-out mice. To clarify the functions of the protein in the brain, we generated two conditional knock-out (cKO) mouse lines: 1) one lacking Caps1 in the forebrain; and 2) the other lacking Caps1 in the cerebellum. Both cKO mouse lines were born normally and grew to adulthood, although they showed subcellular and synaptic abnormalities. Forebrain-specific Caps1 cKO mice showed reduced immunoreactivity for the DCV marker secretogranin II (SgII) and the trans-Golgi network (TGN) marker syntaxin 6, a reduced number of presynaptic DCVs, and dilated trans-Golgi cisternae in the CA3 region. Cerebellum-specific Caps1 cKO mice had decreased immunoreactivity for SgII and brain-derived neurotrophic factor (BDNF) along the climbing fibers. At climbing fiber-Purkinje cell synapses, the number of DCVs was markedly lower and the number of synaptic vesicles was also reduced. Correspondingly, the mean amplitude of EPSCs was decreased, whereas paired-pulse depression was significantly increased. Our results suggest that loss of CAPS1 disrupts the TGN-DCV pathway, which possibly impairs synaptic transmission by reducing the presynaptic release probability.

Original languageEnglish
Pages (from-to)17326-17334
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number44
DOIs
Publication statusPublished - 2013

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Transcription Factor AP-1
Secretory Vesicles
Knockout Mice
Secretogranin II
Brain
trans-Golgi Network
Prosencephalon
Cerebellum
Qa-SNARE Proteins
Synaptic Vesicles
Purkinje Cells
Brain-Derived Neurotrophic Factor
Exocytosis
Synaptic Transmission
Synapses
Cell Count
Parturition
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

CAPS1 deficiency perturbs dense-core vesicle trafficking and golgi structure and reduces presynaptic release probability in the mouse brain. / Sadakata, Tetsushi; Kakegawa, Wataru; Shinoda, Yo; Hosono, Mayu; Katoh-Semba, Ritsuko; Sekine, Yukiko; Sato, Yumi; Tanaka, Mika; Iwasato, Takuji; Itohara, Shigeyoshi; Furuyama, Kenichiro; Kawaguchi, Yoshiya; Ishizaki, Yasuki; Yuzaki, Michisuke; Furuichi, Teiichi.

In: Journal of Neuroscience, Vol. 33, No. 44, 2013, p. 17326-17334.

Research output: Contribution to journalArticle

Sadakata, T, Kakegawa, W, Shinoda, Y, Hosono, M, Katoh-Semba, R, Sekine, Y, Sato, Y, Tanaka, M, Iwasato, T, Itohara, S, Furuyama, K, Kawaguchi, Y, Ishizaki, Y, Yuzaki, M & Furuichi, T 2013, 'CAPS1 deficiency perturbs dense-core vesicle trafficking and golgi structure and reduces presynaptic release probability in the mouse brain', Journal of Neuroscience, vol. 33, no. 44, pp. 17326-17334. https://doi.org/10.1523/JNEUROSCI.2777-13.2013
Sadakata, Tetsushi ; Kakegawa, Wataru ; Shinoda, Yo ; Hosono, Mayu ; Katoh-Semba, Ritsuko ; Sekine, Yukiko ; Sato, Yumi ; Tanaka, Mika ; Iwasato, Takuji ; Itohara, Shigeyoshi ; Furuyama, Kenichiro ; Kawaguchi, Yoshiya ; Ishizaki, Yasuki ; Yuzaki, Michisuke ; Furuichi, Teiichi. / CAPS1 deficiency perturbs dense-core vesicle trafficking and golgi structure and reduces presynaptic release probability in the mouse brain. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 44. pp. 17326-17334.
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AU - Sato, Yumi

AU - Tanaka, Mika

AU - Iwasato, Takuji

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AU - Furuyama, Kenichiro

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