ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The Coffin-Lowry syndrome-associated protein RSK2 regulates neurite outgrowth through phosphorylation of phospholipase D1 (PLD1) and synthesis of phosphatidic acid.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 50 citations in OpenAlex.
- Müller glia derived EVs promote neurite recovery of an enriched population of retinal ganglion like cells derived from hESC retinal organoids after damage.Scientific reports · 2026Article
- Exosome-Mediated Delivery of a PLD1 Modulator Overcomes Bioavailability Hurdles to Target Synaptopathy in Neurodegenerative Diseases.Pharmaceutical research · 2025Article
- Designing New Natural-Mimetic Phosphatidic Acid: A Versatile and Innovative Synthetic Strategy for Glycerophospholipid Research.Angewandte Chemie (International ed. in English) · 2025Article
- Ribosomal S6 kinase signaling regulates neuronal viability during development and confers resistance to excitotoxic cell death in mature neurons.Neuroscience · 2024Article
- Rpsa Signaling Regulates Cortical Neuronal Morphogenesis via Its Ligand, PEDF, and Plasma Membrane Interaction Partner, Itga6.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Saturated free fatty acids and association with memory formation.Nature communications · 2021Article
- The AGCVIII kinase Dw2 modulates cell proliferation, endomembrane trafficking, and MLG/xylan cell wall localization in elongating stem internodes of Sorghum bicolor.The Plant journal : for cell and molecular biology · 2021Article
- Cellular phosphatidic acid sensor, α-synuclein N-terminal domain, detects endogenous phosphatidic acid in macrophagic phagosomes and neuronal growth cones.Biochemistry and biophysics reports · 2020Article
- Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications.Frontiers in cell and developmental biology · 2019Review
- Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology.Frontiers in cellular neuroscience · 2019Review
- Phospholipase D1 Signaling: Essential Roles in Neural Stem Cell Differentiation.Journal of molecular neuroscience : MN · 2018Review
- Animal Models for Coffin-Lowry Syndrome: RSK2 and Nervous System Dysfunction.Frontiers in behavioral neuroscience · 2018Review
- HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels.Nature communications · 2016Article
- Astrocyte-derived phosphatidic acid promotes dendritic branching.Scientific reports · 2016Article
- PLD1 participates in BDNF-induced signalling in cortical neurons.Scientific reports · 2015Article
- Cellular and physiological roles for phospholipase D1 in cancer.The Journal of biological chemistry · 2014Review
- Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis.Cellular logisticsArticle
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
More than 80 human X-linked genes have been associated with mental retardation and deficits in learning and memory. However, most of the identified mutations induce limited morphological alterations in brain organization and the molecular bases underlying neuronal clinical features remain elusive. We show here that neurons cultured from mice lacking ribosomal S6 kinase 2 (Rsk2), a model for the Coffin-Lowry syndrome (CLS), exhibit a significant delay in growth in a similar way to that shown by neurons cultured from phospholipase D1 (Pld1) knock-out mice. We found that gene silencing of Pld1 or Rsk2 as well as acute pharmacological inhibition of PLD1 or RSK2 in PC12 cells strongly impaired neuronal growth factor (NGF)-induced neurite outgrowth. Expression of a phosphomimetic PLD1 mutant rescued the inhibition of neurite outgrowth in PC12 cells silenced for RSK2, revealing that PLD1 is a major target for RSK2 in neurite formation. NGF-triggered RSK2-dependent phosphorylation of PLD1 led to its activation and the synthesis of phosphatidic acid at sites of neurite growth. Additionally, total internal reflection fluorescence microscopy experiments revealed that RSK2 and PLD1 positively control fusion of tetanus neurotoxin insensitive vesicle-associated membrane protein (TiVAMP)/VAMP-7 vesicles at sites of neurite outgrowth. We propose that the loss of function mutations in RSK2 that leads to CLS and neuronal deficits are related to defects in neuronal growth due to impaired RSK2-dependent PLD1 activity resulting in a reduced vesicle fusion rate and membrane supply.
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