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

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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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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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, 33(44), 17326-17334. https://doi.org/10.1523/JNEUROSCI.2777-13.2013