title: Involvement of diacylglycerol kinase β in the spine formation at distal dendrites of striatal medium spiny neurons.
abstract: Spine formation, a salient feature underlying neuronal plasticity to adapt to a changing environment, is regulated by complex machinery involving membrane signal transduction. The diacylglycerol kinase (DGK) family, which is involved in membrane lipid metabolism, catalyzes the phosphorylation of a lipid second messenger, diacylglycerol (DG). Of the DGKs, DGKβ is characterized by predominant expression in a specific brain region: the striatum. We previously demonstrated that DGKβ is expressed selectively in medium spiny neurons (MSNs) and that it is highly enriched in the perisynaptic membrane on dendritic spines contacted with excitatory terminals. Moreover, DGKβ regulates spinogenesis through actin-based remodeling in an activity-dependent manner. However, the detailed mechanisms of spinogenesis regulation and its functional significance remain unclear. To address these issues, we performed Golgi-Cox staining to examine morphological aspects of MSNs in the striatum of DGKβ-knockout (KO) mice. Results show that striatal MSNs of DGKβ-KO mice exhibited lower dendritic spine density at distal dendrites than wild-type mice did. We also sought protein targets that interact with DGKβ and identified the GluA2 AMPA receptor subunit as a novel DGKβ binding partner. In addition, DGKβ-deficient brain exhibits significant reduction of TARP γ-8, which represents a transmembrane AMPA receptor regulatory protein. These findings suggest that DGKβ regulates the spine formation at distal dendrites in MSNs.
authors.affiliation: Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address: yahodumi@med.id.yamagata-u.ac.jp.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Hozumi
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kakefuda
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000201:enzymology*; D049229:Dendritic Spines / Q000201:enzymology*; D019852:Diacylglycerol Kinase / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D019852:Diacylglycerol Kinase; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptor; Diacylglycerol kinase; Distal dendrites; Immunohistochemistry; Immunoprecipitation; Striatum