Cbln1 is essential for synaptic integrity and plasticity in the cerebellum

• Published in: Nature neuroscience Vol. 8; no. 11; pp. 1534 - 1541
• Main Authors: Yuzaki, Michisuke, Morgan, James I, Hirai, Hirokazu, Pang, Zhen, Bao, Dashi, Miyazaki, Taisuke, Li, Leyi, Miura, Eriko, Parris, Jennifer, Rong, Yongqi, Watanabe, Masahiko
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2005
• Subjects: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Ataxia - genetics; Behavior, Animal; Blotting, Northern - methods; Blotting, Western - methods; Cells, Cultured; Cerebellum; Cerebellum - cytology; Cloning, Molecular - methods; Dendritic Spines; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Excitatory Postsynaptic Potentials - physiology; Excitatory Postsynaptic Potentials - radiation effects; Gene Expression Regulation; Humans; In Situ Hybridization - methods; In Vitro Techniques; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Mice; Mice, Inbred ICR; Mice, Transgenic; Microscopy, Electron, Transmission - methods; Motor Activity - genetics; Mutagenesis - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neural transmission; Neuronal Plasticity - physiology; Neurons - physiology; Neurons - ultrastructure; Neuroplasticity; Patch-Clamp Techniques - methods; Physiological aspects; Protein Precursors - genetics; Protein Precursors - physiology; Radioimmunoassay - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Synapses - metabolism; Synapses - ultrastructure; Transfection - methods; Vesicular Glutamate Transport Protein 2 - metabolism; United States; Japan
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1576

Cbln1 is a cerebellum-specific protein of previously unknown function that is structurally related to the C1q and tumor necrosis factor families of proteins. We show that Cbln1 is a glycoprotein secreted from cerebellar granule cells that is essential for three processes in cerebellar Purkinje cells: the matching and maintenance of pre- and postsynaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses. Notably, the phenotype of cbln1-null mice mimics loss-of-function mutations in the orphan glutamate receptor, GluR delta2, a gene selectively expressed in Purkinje neurons. Therefore, Cbln1 secreted from presynaptic granule cells may be a component of a transneuronal signaling pathway that controls synaptic structure and plasticity.