title: Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum.
abstract: Neuronal networks are dynamically modified by selective synapse pruning during development and adulthood. However, how certain connections win the competition with others and are subsequently maintained is not fully understood. Here, we show that C1ql1, a member of the C1q family of proteins, is provided by climbing fibers (CFs) and serves as a crucial anterograde signal to determine and maintain the single-winner CF in the mouse cerebellum throughout development and adulthood. C1ql1 specifically binds to the brain-specific angiogenesis inhibitor 3 (Bai3), which is a member of the cell-adhesion G-protein-coupled receptor family and expressed on postsynaptic Purkinje cells. C1ql1-Bai3 signaling is required for motor learning but not for gross motor performance or coordination. Because related family members of C1ql1 and Bai3 are expressed in various brain regions, the mechanism described here likely applies to synapse formation, maintenance, and function in multiple neuronal circuits essential for important brain functions.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mitakidis
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.affiliation: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Yukari H
authors.initials: YH
authors.lastname: Takeo
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Motohashi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Division of Neurology, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Muramatsu
authors.affiliation: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan; Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: A Radu
authors.initials: AR
authors.lastname: Aricescu
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075, Japan. Electronic address: myuzaki@a5.keio.jp.
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D007858:Learning; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
chemical_list: C484729:Adgrb3 protein, mouse; C000596173:C1ql1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015922:Complement C1q