title: Cbln1 is essential for synaptic integrity and plasticity in the cerebellum.
abstract: 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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, MS 323, Memphis, Tennessee 38105-2794, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Pang
authors.forename: Dashi
authors.initials: D
authors.lastname: Bao
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Leyi
authors.initials: L
authors.lastname: Li
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.forename: Jennifer
authors.initials: J
authors.lastname: Parris
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Rong
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.forename: James I
authors.initials: JI
authors.lastname: Morgan
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001259:Ataxia / Q000235:genetics; D001522:Behavior, Animal; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003001:Cloning, Molecular / Q000379:methods; D049229:Dendritic Spines; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009043:Motor Activity / Q000235:genetics; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection / Q000379:methods; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: C092370:Cbln1 protein, mouse; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C493476:SLC17A6 protein, human; D050599:Vesicular Glutamate Transport Protein 2