Cerebellar regulation mechanisms learned from studies on GluRdelta2

Abstract

The amino acid sequence suggests that glutamate receptor delta2 (GluRdelta2) belongs to an ionotropic GluR (iGluR) subunit family. However, neither the direct binding to glutamate nor the incorporation into any native iGluRs has been demonstrated. One prominent feature of GluRdelta2 is its predominant expression at parallel fiber-Purkinje cell synapses in the cerebellum. Knockdown or knockout of GluRdelta2 impairs synaptic plasticity, stabilization, elimination, motor control, and learning. Therefore, GluRdelta2 plays a crucial role in the cerebellar function. Several ataxic spontaneous mutant mice have defects in the GluRdelta gene. Numerous proteins interacting with GluRdelta2 have been identified. Recent in vivo studies on GluRdelta2 knockout mice shed light on the mechanism by which GluRdelta2 deficiency causes ataxia and unveiled some secondary influence of the GluRdelta2 deficiency on the function of the central nervous system. Studies on GluRdelta2 might provide unique clues regarding not only the molecular mechanism of synaptic regulations but also the functioning mechanism of the entire cerebellar system.