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Brain Res. 2015 Jan 12;1594:36-45. doi: 10.1016/j.brainres.2014.11.012. Epub 2014 Nov 15.

Involvement of diacylglycerol kinase β in the spine formation at distal dendrites of striatal medium spiny neurons.

Author information

1
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address: yahodumi@med.id.yamagata-u.ac.jp.
2
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
3
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
4
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.

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.

KEYWORDS:

AMPA receptor; Diacylglycerol kinase; Distal dendrites; Immunohistochemistry; Immunoprecipitation; Striatum

PMID:
25446448
DOI:
10.1016/j.brainres.2014.11.012
[Indexed for MEDLINE]

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