Characterization of the δ2 glutamate receptor-binding protein delphilin

Splicing variants with differential palmitoylation and an additional PDZ domain

Keiko Matsuda, Shinji Matsuda, Clare M. Gladding, Michisuke Yuzaki

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The glutamate receptor δ2 (GluR δ2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluRδ2 functions remains unclear, its lack of channel activity and its role in controlling the endocytosis of δ-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors have suggested that GluRδ2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluRδ2, 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 Ldelphilin. 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 GluRδ2 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 GluRδ2 pools and may control GluRδ2 signaling in Purkinje cells.

Original languageEnglish
Pages (from-to)25577-25587
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number35
DOIs
Publication statusPublished - 2006 Sep 1

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Protein Splicing
Lipoylation
PDZ Domains
Glutamate Receptors
Carrier Proteins
Purkinje Cells
Protein Isoforms
delphilin
Dendritic Spines
Neuronal Plasticity
AMPA Receptors
Fibers
COS Cells
Carisoprodol
Cell membranes
Endocytosis
Synapses
Neurons
Plasticity
Cluster Analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Characterization of the δ2 glutamate receptor-binding protein delphilin: Splicing variants with differential palmitoylation and an additional PDZ domain",
abstract = "The glutamate receptor δ2 (GluR δ2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluRδ2 functions remains unclear, its lack of channel activity and its role in controlling the endocytosis of δ-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors have suggested that GluRδ2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluRδ2, 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 Ldelphilin. 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 GluRδ2 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 GluRδ2 pools and may control GluRδ2 signaling in Purkinje cells.",
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T1 - Characterization of the δ2 glutamate receptor-binding protein delphilin

T2 - Splicing variants with differential palmitoylation and an additional PDZ domain

AU - Matsuda, Keiko

AU - Matsuda, Shinji

AU - Gladding, Clare M.

AU - Yuzaki, Michisuke

PY - 2006/9/1

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N2 - The glutamate receptor δ2 (GluR δ2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluRδ2 functions remains unclear, its lack of channel activity and its role in controlling the endocytosis of δ-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors have suggested that GluRδ2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluRδ2, 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 Ldelphilin. 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 GluRδ2 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 GluRδ2 pools and may control GluRδ2 signaling in Purkinje cells.

AB - The glutamate receptor δ2 (GluR δ2) is predominantly expressed at parallel fiber-Purkinje cell postsynapses and plays crucial roles in synaptogenesis and synaptic plasticity. Although the mechanism by which GluRδ2 functions remains unclear, its lack of channel activity and its role in controlling the endocytosis of δ-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors have suggested that GluRδ2 may convey signals by interacting with intracellular signaling molecules. Among several proteins that interact with GluRδ2, 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 Ldelphilin. 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 GluRδ2 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 GluRδ2 pools and may control GluRδ2 signaling in Purkinje cells.

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