Anterograde C1ql1 Signaling Is Required in Order to Determine and Maintain a Single-Winner Climbing Fiber in the Mouse Cerebellum

• DOI: 10.1016/j.neuron.2014.12.020
• Publication Date: 2015-01-21T19:06:37Z
• Authors: Wataru Kakegawa; Nikolaos Mitakidis; Eriko Miura; Manabu Abe; Keiko Matsuda; Yukari H. Takeo; Kazuhisa Kohda; Junko Motohashi; Akiyo Takahashi; Soichi Nagao; Shin-ichi Muramatsu; Masahiko Watanabe; Kenji Sakimura; A. Radu Aricescu; Michisuke Yuzaki
• Keywords: 0303 health sciences; Neuroscience(all); Complement C1q; Membrane Proteins; Nerve Tissue Proteins; Motor Activity; Mice; Purkinje Cells; 03 medical and health sciences; Cerebellum; Synapses; Animals; Learning; Signal Transduction

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.