Characterization of the δ2 glutamate receptor-binding protein delphilin -: Splicing variants with differential palmitoylation and an additional PDZ domain

The glutamate receptor delta 2 (GluR delta 2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluR delta 2 functions remains unclear, its lack of channel activity and its role in controlling the endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ( AMPA) receptors have suggested that GluR delta 2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluR delta 2, delphilin is unique in that it is selectively expressed at parallel fiber-Purkinje cell synapses and that, in addition to a single PDZ domain, it contains a formin homology domain that is thought to regulate actin dynamics. Here, we report a new isoform of delphilin, designated as L-delphilin, that has alternatively spliced N-terminal exons encoding an additional PDZ domain. Although original delphilin, designated S-delphilin, was palmitoylated at the N terminus, this region was spliced out in L-delphilin. As a result, S-delphilin was associated with plasma membranes in COS cells and dendritic spines in hippocampal neurons, whereas L-delphilin formed clusters in soma and dendritic shafts. In addition, S-delphilin, but not L-delphilin, facilitated the expression of GluR delta 2 on the cell surface. These results indicate that, like PSD-95 and GRIP/ABP, delphilin isoforms with differential palmitoylation and clustering capabilities may provide two separate intracellular and surface GluR delta 2 pools and may control GluR delta 2 signaling in Purkinje cells.