ArticleThe Journal of biological chemistry2011
Phospholipase Cdelta3 regulates RhoA/Rho kinase signaling and neurite outgrowth.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Phospholipases: Paving the Way for a New Life.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- PLCD3 inhibits apoptosis and promotes proliferation, invasion and migration in gastric cancer.Discover oncology · 2024Article
- LncRNA-mediated ceRNA network reveals the mechanism of action of Saorilao-4 decoction against pulmonary fibrosis.Frontiers in genetics · 2024Article
- Leptin Induces MMP-1 Expression Through the RhoA/ERK1/2/NF-κB Axis in Human Intervertebral Disc Cartilage Endplate-Derived Stem Cells.Journal of inflammation research · 2023Article
- Context-Dependent Role of miR-124 in Retinoic Acid-Induced Growth Cone Attraction of Regenerating Motorneurons.Cellular and molecular neurobiology · 2022Article
- ATF5 deficiency causes abnormal cortical development.Scientific reports · 2021Article
- Review
- Hyaluronic acid induces ROCK-dependent amoeboid migration in glioblastoma cells.Biomaterials science · 2020Article
- Influence of spatially segregated IPProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Phospholipase C.Advances in experimental medicine and biology · 2020Review
- Acute Proteomic Changes in the Lung After WTLI in a Mouse Model: Identification of Potential Initiating Events for Delayed Effects of Acute Radiation Exposure.Health physics · 2019Article
- PLCD3, a flotillin2-interacting protein, is involved in proliferation, migration and invasion of nasopharyngeal carcinoma cells.Oncology reports · 2018Article
- Phospholipase C-η2 interacts with nuclear and cytoplasmic LIMK-1 during retinoic acid-stimulated neurite growth.Histochemistry and cell biology · 2016Article
- Critical roles of Gi/o proteins and phospholipase C-δ1 in the activation of receptor-operated TRPC4 channels.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C.SpringerPlus · 2016Article
- Simultaneous loss of phospholipase Cδ1 and phospholipase Cδ3 causes cardiomyocyte apoptosis and cardiomyopathy.Cell death & disease · 2014Article
- HIV-1 Tat protein perturbs diacylglycerol production at the plasma membrane of neurosecretory cells during exocytosis.Communicative & integrative biology · 2013Article
- Phosphoinositides: tiny lipids with giant impact on cell regulation.Physiological reviews · 2013Review
- Rho kinase: A new target for treatment of cerebral ischemia/reperfusion injury.Neural regeneration research · 2013Article
- Invasive cells in animals and plants: searching for LECA machineries in later eukaryotic life.Biology direct · 2013Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipase Cδ3 (PLCδ3) is a key enzyme regulating phosphoinositide metabolism; however, its physiological function remains unknown. Because PLCδ3 is highly enriched in the cerebellum and cerebral cortex, we examined the role of PLCδ3 in neuronal migration and outgrowth. PLCδ3 knockdown (KD) inhibits neurite formation of cerebellar granule cells, and application of PLCδ3KD using in utero electroporation in the developing brain results in the retardation of the radial migration of neurons in the cerebral cortex. In addition, PLCδ3KD inhibits axon and dendrite outgrowth in primary cortical neurons. PLCδ3KD also suppresses neurite formation of Neuro2a neuroblastoma cells induced by serum withdrawal or treatment with retinoic acid. This inhibition is released by the reintroduction of wild-type PLCδ3. Interestingly, the H393A mutant lacking phosphatidylinositol 4,5-bisphosphate hydrolyzing activity generates supernumerary protrusions, and a constitutively active mutant promotes extensive neurite outgrowth, indicating that PLC activity is important for normal neurite outgrowth. The introduction of dominant negative RhoA (RhoA-DN) or treatment with Y-27632, a Rho kinase-specific inhibitor, rescues the neurite extension in PLCδ3KD Neuro2a cells. Similar effects were also detected in primary cortical neurons. Furthermore, the RhoA expression level was significantly decreased by serum withdrawal or retinoic acid in control cells, although this decrease was not observed in PLCδ3KD cells. We also found that exogenous expression of PLCδ3 down-regulated RhoA protein, and constitutively active PLCδ3 promotes the RhoA down-regulation more significantly than PLCδ3 upon differentiation. These results indicate that PLCδ3 negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and thereby promotes neurite extension.
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Registered trials
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