ArticleProceedings of the National Academy of Sciences of the United States of America2001
A role for phospholipase D1 in neurotransmitter release.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 168 citations in OpenAlex.
- Exploring the PLD1-tau interaction in Frontotemporal Dementia.bioRxiv : the preprint server for biology · 2026Article
- Phospholipase D1 produces phosphatidic acid at sites of secretory vesicle docking and fusion.Molecular biology of the cell · 2024Article
- The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.The EMBO journal · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- Article
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- Lipids and Secretory Vesicle Exocytosis.Advances in neurobiology · 2023Article
- Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.International journal of molecular sciences · 2020Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle.Frontiers in molecular neuroscience · 2020Article
- Suppressing aberrant phospholipase D1 signaling in 3xTg Alzheimer's disease mouse model promotes synaptic resilience.Scientific reports · 2019Article
- Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications.Frontiers in cell and developmental biology · 2019Review
- Mechanism of membrane fusion: protein-protein interaction and beyond.International journal of physiology, pathophysiology and pharmacology · 2019Review
- Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology.Frontiers in cellular neuroscience · 2019Review
- The Dual Function of the Polybasic Juxtamembrane Region of Syntaxin 1A in Clamping Spontaneous Release and Stimulating CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Elevated phospholipase D isoform 1 in Alzheimer's disease patients' hippocampus: Relevance to synaptic dysfunction and memory deficits.Alzheimer's & dementia (New York, N. Y.) · 2018Article
- Phosphatidic acid-producing enzymes regulating the synaptic vesicle cycle: Role for PLD?Advances in biological regulation · 2018Review
- PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage.Scientific reports · 2017Article
- Phosphatidic acid and neurotransmission.Advances in biological regulation · 2017Review
- Amygdala-Hippocampal Phospholipase D (PLD) Signaling As Novel Mechanism of Cocaine-Environment Maladaptive Conditioned Responses.The international journal of neuropsychopharmacology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Phosphatidic acid produced by phospholipase D (PLD) as a result of signaling activity is thought to play a role in membrane vesicle trafficking, either as an intracellular messenger or as a cone-shaped lipid that promotes membrane fusion. We recently described that, in neuroendocrine cells, plasma membrane-associated PLD1 operates at a stage of Ca(2+)-dependent exocytosis subsequent to cytoskeletal-mediated recruitment of secretory granules to exocytotic sites. We show here that PLD1 also plays a crucial role in neurotransmitter release. Using purified rat brain synaptosomes subjected to hypotonic lysis and centrifugation, we found that PLD1 is associated with the particulate fraction containing the plasma membrane. Immunostaining of rat cerebellar granule cells confirmed localization of PLD1 at the neuronal plasma membrane in zones specialized for neurotransmitter release (axonal neurites, varicosities, and growth cone-like structures). To determine the potential involvement of PLD1 in neurotransmitter release, we microinjected catalytically inactive PLD1(K898R) into Aplysia neurons and analyzed its effects on evoked acetylcholine (ACh) release. PLD1(K898R) produced a fast and potent dose-dependent inhibition of ACh release. By analyzing paired-pulse facilitation and postsynaptic responses evoked by high-frequency stimulations, we found that the exocytotic inhibition caused by PLD1(K898R) was not the result of an alteration in stimulus-secretion coupling or in vesicular trafficking. Analysis of the fluctuations in amplitude of the postsynaptic responses revealed that the PLD1(K898R) blocked ACh release by reducing the number of active presynaptic-releasing sites. Our results provide evidence that PLD1 plays a major role in neurotransmission, most likely by controlling the fusogenic status of presynaptic release sites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.