PMID- 24174665 OWN - NLM STAT- MEDLINE DCOM- 20131223 LR - 20211021 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 33 IP - 44 DP - 2013 Oct 30 TI - CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain. PG - 17326-34 LID - 10.1523/JNEUROSCI.2777-13.2013 [doi] AB - 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. FAU - Sadakata, Tetsushi AU - Sadakata T AD - Advanced Scientific Research Leaders Development Unit and Department of Molecular and Cellular Neurobiology, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan, Japan Science and Technology Agency/Core Research for Evolutional Science and Technology, Kawaguchi, Saitama 332-0012, Japan, Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan, Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan, Graduate School of Medical Science, Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan, Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan, Laboratory for Behavioral Genetics, Funding Program for World-Leading Innovative R&D on Science and Technology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan, Department of Developmental Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan, and Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan. FAU - Kakegawa, Wataru AU - Kakegawa W FAU - Shinoda, Yo AU - Shinoda Y FAU - Hosono, Mayu AU - Hosono M FAU - Katoh-Semba, Ritsuko AU - Katoh-Semba R FAU - Sekine, Yukiko AU - Sekine Y FAU - Sato, Yumi AU - Sato Y FAU - Tanaka, Mika AU - Tanaka M FAU - Iwasato, Takuji AU - Iwasato T FAU - Itohara, Shigeyoshi AU - Itohara S FAU - Furuyama, Kenichiro AU - Furuyama K FAU - Kawaguchi, Yoshiya AU - Kawaguchi Y FAU - Ishizaki, Yasuki AU - Ishizaki Y FAU - Yuzaki, Michisuke AU - Yuzaki M FAU - Furuichi, Teiichi AU - Furuichi T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Cadps protein, mouse) RN - 0 (Calcium-Binding Proteins) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Animals MH - Brain/*metabolism/ultrastructure MH - Calcium-Binding Proteins/*deficiency MH - Golgi Apparatus/*metabolism/ultrastructure MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nerve Tissue Proteins/*deficiency MH - Presynaptic Terminals/*metabolism/ultrastructure MH - Probability MH - Protein Transport/genetics MH - Secretory Vesicles/*metabolism/ultrastructure PMC - PMC6618362 EDAT- 2013/11/01 06:00 MHDA- 2013/12/24 06:00 PMCR- 2014/04/30 CRDT- 2013/11/01 06:00 PHST- 2013/11/01 06:00 [entrez] PHST- 2013/11/01 06:00 [pubmed] PHST- 2013/12/24 06:00 [medline] PHST- 2014/04/30 00:00 [pmc-release] AID - 33/44/17326 [pii] AID - 2777-13 [pii] AID - 10.1523/JNEUROSCI.2777-13.2013 [doi] PST - ppublish SO - J Neurosci. 2013 Oct 30;33(44):17326-34. doi: 10.1523/JNEUROSCI.2777-13.2013.