ArticleThe EMBO journal2022
Autophagy regulates neuronal excitability by controlling cAMP/protein kinase A signaling at the synapse.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Synaptic proteomics identifies cathepsin B as a regulator of synapse remodelling during learning.bioRxiv : the preprint server for biology · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Schizophrenia and bipolar disorder risk gene AKAP11 sustains cognitive function by regulating TFEB-mediated autophagy.Cell death and differentiation · 2026Article
- The intrinsic excitability of and autophagy protein expression levels in dentate gyrus ensembles regulate fear generalization.Neural regeneration research · 2026Article
- Autophagic Pathway on GABARAP Involved in GABANeurochemical research · 2026Review
- Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Article
- The Role of HIF-1α/BNIP3 Pathway in Hippocampal Neuronal Autophagy in Epilepsy.Molecular neurobiology · 2025Article
- Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo.Nature communications · 2025Article
- Chaperone-mediated autophagy regulates neuronal activity by sex-specific remodelling of the synaptic proteome.Nature cell biology · 2025Article
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Transcranial iTBS Combined With Trans-Spinal iTBS Targeting PDE1A/cAMP/PKA Axis Regulates Neural Regeneration After Spinal Cord Injury.CNS neuroscience & therapeutics · 2025Article
- Autophagosomes anchor an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling.The EMBO journal · 2025Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.Nature metabolism · 2025Article
- Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis inAutophagy · 2025Article
- Turning garbage into gold: Autophagy in synaptic function.Current opinion in neurobiology · 2025Review
- The senescent synapse: A look at autophagy, calcium handling, and mitochondrial bioenergetics at the synapse in ageing and Parkinson's disease.Current research in physiology · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy provides nutrients during starvation and eliminates detrimental cellular components. However, accumulating evidence indicates that autophagy is not merely a housekeeping process. Here, by combining mouse models of neuron-specific ATG5 deficiency in either excitatory or inhibitory neurons with quantitative proteomics, high-content microscopy, and live-imaging approaches, we show that autophagy protein ATG5 functions in neurons to regulate cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of a synapse-confined proteome. This function of ATG5 is independent of bulk turnover of synaptic proteins and requires the targeting of PKA inhibitory R1 subunits to autophagosomes. Neuronal loss of ATG5 causes synaptic accumulation of PKA-R1, which sequesters the PKA catalytic subunit and diminishes cAMP/PKA-dependent phosphorylation of postsynaptic cytoskeletal proteins that mediate AMPAR trafficking. Furthermore, ATG5 deletion in glutamatergic neurons augments AMPAR-dependent excitatory neurotransmission and causes the appearance of spontaneous recurrent seizures in mice. Our findings identify a novel role of autophagy in regulating PKA signaling at glutamatergic synapses and suggest the PKA as a target for restoration of synaptic function in neurodegenerative conditions with autophagy dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.