Abstract
The delta2 glutamate receptor (GluRdelta2), which is predominantly expressed at distal dendrites of cerebellar Purkinje cells, plays a crucial role in cerebellar functions; mutant mice deficient in GluRdelta2 (delta2−/−) impair synapse formation and long-term depression (LTD) in the cerebellum, and consequently lead to motor discoordination. However, a fundamental question whether GluRdelta2 is activated by glutamate analogues has remained elusive. To address this issue, we here introduced a GluRdelta2 transgene, which had a mutation (Arg514Lys) in the putative ligand-binding motif conserved in all mammalian ionotropic glutamate receptors (iGluRs) and their ancestral bacterial periplasmic amino acid-binding proteins, into delta2−/− mice. Surprisingly, a mutant GluRdelta2 transgene, as well as a wild-type GluRdelta2 transgene, completely rescued the abnormal phenotypes of delta2−/− mice: motor discoordination, multiple climbing fiber innervation, parallel fiber spine morphology, and impaired LTD. Thus, these results indicate that the conserved arginine residue, which is crucial for the binding of iGluRs to glutamate analogues, is not essential for the restoration of GluRdelta2 functions in delta2−/− mice. [Jpn J Physiol 55 Suppl:S133 (2005)]
