title: CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus.
abstract: Calcium-dependent activator protein for secretion 1 (CAPS1) regulates exocytosis of dense-core vesicles in neuroendocrine cells and of synaptic vesicles in neurons. However, the synaptic function of CAPS1 in the mature brain is unclear because Caps1 knockout (KO) results in neonatal death. Here, using forebrain-specific Caps1 conditional KO (cKO) mice, we demonstrate, for the first time, a critical role of CAPS1 in adult synapses. The amplitude of synaptic transmission at CA3-CA1 synapses was strongly reduced, and paired-pulse facilitation was significantly increased, in acute hippocampal slices from cKO mice compared with control mice, suggesting a perturbation in presynaptic function. Morphological analysis revealed an accumulation of synaptic vesicles in the presynapse without any overall morphological change. Interestingly, however, the percentage of docked vesicles was markedly decreased in the Caps1 cKO. Taken together, our findings suggest that CAPS1 stabilizes the state of readily releasable synaptic vesicles, thereby enhancing neurotransmitter release at hippocampal synapses.
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.|School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Shinoda
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ishii
authors.affiliation: Department of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Sadakata
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Division of Neurogenetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.|Department of Genetics, SOKENDAI, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*
chemical_list: C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents