Characterization of the delta2 glutamate receptor-binding protein delphilin: Splicing variants with differential palmitoylation and an additional PDZ domain.
The glutamate receptor delta2 (GluRdelta2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluRdelta2 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 GluRdelta2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluRdelta2, 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 GluRdelta2 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 GluRdelta2 pools and may control GluRdelta2 signaling in Purkinje cells.
Matsuda
Keiko
K
Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Matsuda
Shinji
S
Gladding
Clare M
CM
Yuzaki
Michisuke
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D019308:Palmitic Acid / Q000737:chemistry*; D011485:Protein Binding; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry; D017470:Receptors, Glutamate / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C447759:delphilin; C107913:glutamate receptor delta 2; D019308:Palmitic Acid