PLD4 Is Involved in Phagocytosis of Microglia: Expression and Localization Changes of PLD4 Are Correlated with Activation State of Microglia

Phospholipase D4 (PLD4) is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1)-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidyl...

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Bibliographic Details
Published in:PloS one 2011-11, Vol.6 (11), p.e27544
Main Authors: Otani, Yoshinori, Yamaguchi, Yoshihide, Sato, Yumi, Furuichi, Teiichi, Ikenaka, Kazuhiro, Kitani, Hiroshi, Baba, Hiroko
Format: Article
Language:English
Subjects:
Adapters
Biology
Calcium
Cell growth
Cerebellum
Choline
Developmental stages
Enzymatic activity
Enzymes
Fibroblasts
Gene expression
Growth factors
Immunoglobulins
Kinases
Lecithin
Life sciences
Lipopolysaccharides
Localization
Microglia
Mitogens
Nervous system
Neurobiology
Neurosciences
Nuclei
Nuclei (cytology)
Nucleoli
Phagocytosis
Phagosomes
Pharmacy
Phosphatidic acid
Phosphatidylcholine
Phospholipase
Phospholipases
Phosphorylation
Physiology
Proteins
Ribonucleic acid
RNA
Rodents
siRNA
Substantia alba
Transcription factors
Tumor necrosis factor-TNF
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Summary:Phospholipase D4 (PLD4) is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1)-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidylcholine into choline and phosphatidic acid, and its function is completely unknown. In the present study, we examined the distribution of PLD4 in mouse cerebellar white matter during development and under pathological conditions. Immunohistochemical analysis revealed that PLD4 expression was associated with microglial activation under such two different circumstances. A primary cultured microglia and microglial cell line (MG6) showed that PLD4 was mainly present in the nucleus, except the nucleolus, and expression of PLD4 was upregulated by lipopolysaccharide (LPS) stimulation. In the analysis of phagocytosis of LPS-stimulated microglia, PLD4 was co-localized with phagosomes that contained BioParticles. Inhibition of PLD4 expression using PLD4 specific small interfering RNA (siRNA) in MG6 cells significantly reduced the ratio of phagocytotic cell numbers. These results suggest that the increased PLD4 in the activation process is involved in phagocytosis of activated microglia in the developmental stages and pathological conditions of white matter.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027544