Abstract
Cbln1 is the prototype for a family of four brain-specific proteins (Cbln1-Cbln4) of unknown function that was first identified by virtue of its harboring a naturally occurring 16 amino acid peptide, cerebellin. Cbln1 is a cerebellum-specific protein and structurally related to the C1q and Tumor Necrosis Factor families of proteins. We show here that Cbln1 is secreted from cerebellar granule cells as a glycoprotein and is essential for three processes in cerebellar Purkinje cells: the matching and maintenance of pre- and post-synaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and the induction of long-term depression at parallel fiber-Purkinje cell synapses. Interestingly, the behavioral, physiological and anatomical phenotype of cbln1-null mice precisely 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 previously undocumented trans-neuronal signaling pathway that controls synaptic structure and plasticity. [J Physiol Sci. 2006;56 Suppl:S167]
