期刊
JOURNAL OF NEUROSCIENCE
卷 33, 期 44, 页码 17326-17334出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2777-13.2013
关键词
-
资金
- Japan Foundation for Neuroscience and Mental Health
- Uehara Memorial Foundation
- Takeda Science Foundation
- Nakajima Foundation
- Yamada Science Foundation
- Mother and Child Health Foundation
- NOVARTIS Foundation for the Promotion of Science
- Inamori Foundation, Scientific Research on Innovative Areas Foundation of Synapse and Neurocircuit Pathology,
- CREST
- FIRST program of the Japan Science and Technology Agency, Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [25110707]
- Japan Society for the Promotion of Science [25430061]
- Institute of Physical and Chemical Research (RIKEN Brain Science Institute)
- Grants-in-Aid for Scientific Research [23689012, 25110707, 25430061, 23300137, 23240062] Funding Source: KAKEN
Ca2+-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据