ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
APT1-Mediated Depalmitoylation Regulates Hippocampal Synaptic Plasticity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Unraveling the enigma: Post-translational modifications in psychiatric disorders and their regulatory mechanisms.Journal of translational internal medicine · 2026Article
- Sex-dependent rescue of memory and synaptic deficits in AD model mice by increasing PSD-95 palmitoylation.Communications biology · 2026Article
- Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity.Cellular and molecular life sciences : CMLS · 2025Article
- Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- ZDHHC4 Influences Obsessive-Compulsive Disorder Risk Through Imaging-Derived Phenotypes: A Mendelian Randomization Study.Journal of molecular neuroscience : MN · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- The ROCK Inhibitor Fasudil and Sertraline Share Morphological and Molecular Effects in the Hippocampus of Chronically Stressed Rats: Exploring Common Antidepressant Pathways by Network Pharmacology.ACS pharmacology & translational science · 2025Article
- Zhinao Capsule Improved Sleep and Memory Disorders in APP/PS1 Mice via cAMP/PKA/CREB Signaling Pathway Modulation.Drug design, development and therapy · 2025Article
- Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception.EMBO reports · 2025Article
- Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Article
- Editorial: Role of protein palmitoylation in synaptic plasticity and neuronal differentiation, volume II.Frontiers in synaptic neuroscience · 2024Article
- Advances of Protein Palmitoylation in Tumor Cell Deaths.Cancers · 2023Review
- DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus.iScience · 2023Article
- Review
- Activity-dependent post-translational regulation of palmitoylating and depalmitoylating enzymes in the hippocampus.Journal of cell science · 2023Article
- S-Palmitoylation of Synaptic Proteins in Neuronal Plasticity in Normal and Pathological Brains.Cells · 2023Review
- Lost in traffic: consequences of altered palmitoylation in neurodegeneration.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity. Our results showed that global palmitoylation level, palmitoylation of PSD-95 and glutamate receptors, postsynapse density localization of PSD-95, surface expression of AMPARs, and synaptic strength of cultured hippocampal neurons were all enhanced by TTX pretreatment, and these can be reversed by inhibition of palmitoylation with palmitoyl acyl transferases inhibitors, 2-bromopalmitate and N-(tert-butyl) hydroxylamine hydrochloride. Importantly, we also found that acyl-protein thioesterase 1 (APT1)-mediated depalmitoylation is involved in palmitoylation of PSD-95 and glutamatergic synaptic transmission. Knockdown of APT1, not protein palmitoyl thioesterase 1, with shRNA, or selective inhibition, significantly increased AMPAR-mediated synaptic strength, palmitoylation levels, and synaptic or surface expression of PSD-95 and AMPARs. Results from hippocampal tissues and fear-conditioned rats showed that palmitoylation is required for synaptic strengthening and fear memory formation. These results suggest that palmitoylation and APT1-mediated depalmitoylation have critical effects on the regulation of glutamatergic synaptic plasticity, and it may serve as a potential target for learning and memory-associated disorders.
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Registered trials
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.