Cbln1 is essential for synaptic integrity and plasticity in the cerebellum

Nat Neurosci. 2005 Nov;8(11):1534-41. doi: 10.1038/nn1576. Epub 2005 Oct 23.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Ataxia / genetics
  • Behavior, Animal
  • Blotting, Northern / methods
  • Blotting, Western / methods
  • Cells, Cultured
  • 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*
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques / methods
  • Protein Precursors / genetics
  • Protein Precursors / physiology*
  • RNA, Messenger / metabolism
  • Radioimmunoassay / methods
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Transfection / methods
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Cbln1 protein, mouse
  • Nerve Tissue Proteins
  • Protein Precursors
  • RNA, Messenger
  • SLC17A6 protein, human
  • Vesicular Glutamate Transport Protein 2