ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Pumilio-2 regulates translation of Nav1.6 to mediate homeostasis of membrane excitability.
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 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Homeostatic preservation of action potential waveform by Notch and Nerfin-1.Current biology : CB · 2026Article
- A scaffold attachment factor PHM-2 regulates synaptic transmission through SLO-2 potassium channel in C. elegans.PLoS genetics · 2026Article
- Article
- A scaffold attachment factor PHM-2 regulates synaptic transmission through SLO-2 potassium channel inbioRxiv : the preprint server for biology · 2025Article
- Ectopic sodium channel expression decreases excitability of Drosophila Kenyon cells.The Journal of physiology · 2025Article
- Regulation of synapse density by Pumilio RNA-binding proteins.Cell reports · 2024Article
- Characterization of NaLife science alliance · 2024Article
- Article
- RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration.International journal of molecular sciences · 2022Review
- Targeting firing rate neuronal homeostasis can prevent seizures.Disease models & mechanisms · 2022Article
- Mechanisms Driving the Emergence of Neuronal Hyperexcitability in Fragile X Syndrome.International journal of molecular sciences · 2022Review
- The role of altered translation in intellectual disability and epilepsy.Progress in neurobiology · 2022Review
- Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay.Nature communications · 2022Article
- Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in the hippocampal CA3 circuit.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Pumilio2 Promotes Growth of Mature Neurons.International journal of molecular sciences · 2021Article
- Unique repression domains of Pumilio utilize deadenylation and decapping factors to accelerate destruction of target mRNAs.Nucleic acids research · 2020Article
- Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules.Biomolecules · 2020Review
- Functions, mechanisms and regulation of Pumilio/Puf family RNA binding proteins: a comprehensive review.Molecular biology reports · 2020Review
- Pumilio Regulates Sleep Homeostasis in Response to Chronic Sleep Deprivation inFrontiers in neuroscience · 2020Article
- Myocyte enhancer factor-2 and p300 interact to regulate the expression of homeostatic regulator Pumilio in Drosophila.The European journal of neuroscience · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The ability to regulate intrinsic membrane excitability, to maintain consistency of action potential firing, is critical for stable neural circuit activity. Without such mechanisms, Hebbian-based synaptic plasticity could push circuits toward activity saturation or, alternatively, quiescence. Although now well documented, the underlying molecular components of these homeostatic mechanisms remain poorly understood. Recent work in the fruit fly, Drosophila melanogaster, has identified Pumilio (Pum), a translational repressor, as an essential component of one such mechanism. In response to changing synaptic excitation, Pum regulates the translation of the voltage-gated sodium conductance, leading to a concomitant adjustment in action potential firing. Although similar homeostatic mechanisms are operational in mammalian neurons, it is unknown whether Pum is similarly involved. In this study, we report that Pum2 is indeed central to the homeostatic mechanism regulating membrane excitability in rat visual cortical pyramidal neurons. Using RNA interference, we observed that loss of Pum2 leads to increased sodium current (I(Na)) and action potential firing, mimicking the response by these neurons to being deprived of synaptic depolarization. In contrast, increased synaptic depolarization results in increased Pum2 expression and subsequent reduction in INa and membrane excitability. We further show that Pum2 is able to directly bind the predominant voltage-gated sodium channel transcript (NaV1.6) expressed in these neurons and, through doing so, regulates translation of this key determinant of membrane excitability. Together, our results show that Pum2 forms part of a homeostatic mechanism that matches membrane excitability to synaptic depolarization in mammalian neurons.
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