An orphan ionotropic glutamate receptor: The δ2 subunit

The glutamate receptor δ2 (GluRδ2) subunit has been classified as an ionotropic glutamate receptor on the basis of the amino acid sequence. It is considered an orphan receptor since no physiological ligand has so far been identified. GluRδ2 is selectively localized at the parallel fiber–Purkinje cell (PF–PC) synapses in the adult cerebellar cortex, where it promotes and maintains the integrity of these synapses. Mutations of the gene coding for the GluRδ2 are also accompanied by reduced regression of the climbing fiber (CF) multiple innervation, loss of long term depression (LDT) and by specific cerebellar dysfunctions involving motor coordination, motor learning and impairment of fear memory consolidation. In addition, it participates in the competition between heterologous afferent fibers to PCs. On the whole, it appears that during evolution GluRδ2 has lost its channel properties to acquire the function of an activity-dependent adhesion molecule with the key role of orchestrating the architecture of the PC innervation to allow two different patterns of signal elaboration; the CF all-or-none depolarization in the proximal dendritic domain and a highly discriminative capacity in the distal domain.