The delta2 glutamate receptor: 10 years later.

The orphan glutamate receptor delta2 (GluRdelta2) is predominantly expressed in Purkinje cells and plays a crucial role in cerebellar functions: mice that lack the GluRdelta2 gene display ataxia and impaired synaptic plasticity. However, when expressed alone or with other glutamate receptors, GluRdelta2 does not form functional glutamate-gated ion channels nor does it bind to glutamate analogs. Therefore, the mechanisms by which GluRdelta2 participates in cerebellar functions have been elusive. Studies of mutant mice such as lurcher, hotfoot, and GluRdelta2 knockout mice have provided clues to the structure and function of GluRdelta2. GluRdelta2 has a channel pore similar to that of other glutamate receptors; the channel is functional at least when the lurcher mutation is present. GluRdelta2 must be transported to the Purkinje cell surface to function; the absence of surface GluRdelta2 causes the ataxic phenotype of hotfoot mice. In GluRdelta2-null mice, the presence of naked spines not innervated by parallel fibers may influence the sustained innervation of mutant Purkinje cells by multiple climbing fibers. From these results, several hypotheses about mechanisms by which GluRdelta2 functions are proposed in this article. Further characterization of GluRdelta2's functions will provide key insights into normal and abnormal cerebellar functions.