Characterization of trans-neuronal trafficking of Cbln1

Cbln1, a glycoprotein secreted from granule cells and GluRδ2 in the postsynaptic densities of Purkinje cells are components of an incompletely understood pathway essential for integrity and plasticity of parallel fiber-Purkinje cell synapses. We show that Cbln1 undergoes anterograde transport from granule cells to Purkinje cells and Bergmann glia, and enters the endolysosomal trafficking system, raising the possibility that Cbln1 exerts its activity on or within Purkinje cells and Bergmann glia. Cbln1 is absent in Purkinje cells and Bergmann glia of GluRδ2-null mice, suggesting a mechanistic convergence on Cbln1 trafficking. Ectopic expression of Cbln1 in Purkinje cells of L7-cbln1 transgenic mice reveals Cbln1 undergoes anterograde and retrograde trans-neuronal trafficking even across synapses that lack GluRΔ2, indicating that it is not universally essential for Cbln1 transport. The L7-cbln1 transgene also ameliorates the locomotor deficits of cbln1-null mice, indicating that the presence and/or release of Cbln1 from the postsynaptic neuron has functional consequences.