Related Experiment Video
Updated: Feb 5, 2026
Microtransplantation of Synaptic Membranes to Reactivate Human Synaptic Receptors for Functional Studies
Published on: July 20, 2022
Pumilio2 regulates synaptic plasticity via translational repression of synaptic receptors in mice
Hongxin Dong1, Mengyi Zhu2, Liping Meng1
1Departments of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Abstract:
PUMILIO 2 (PUM2) is a member of Pumilio and FBF (PUF) family, an RNA binding protein family with phylogenetically conserved roles in germ cell development. The Drosophila Pumilio homolog is also required for dendrite morphogenesis and synaptic function via translational control of synaptic proteins, such as glutamate receptors, and recent mammalian studies demonstrated a similar role in neuronal culture with associated motor and memory abnormalities in vivo. Importantly, transgenic mice with PUM2 knockout show prominent epileptiform activity, and patients with intractable temporal lobe epilepsy and mice with pilocarpine-induced seizures have decreased neuronal PUM2, possibly leading to further seizure susceptibility. However, how PUM2 influences synaptic function in vivo and, subsequently, seizures is not known. We found that PUM2 is highly expressed in the brain, especially in the temporal lobe, and knockout of Pum2 (Pum2 ) resulted in significantly increased pyramidal cell dendrite spine and synapse density. In addition, multiple proteins associated with excitatory synaptic function, including glutamate receptor 2 (GLUR2), are up-regulated in Pum2 mice. The expression of GLUR2 protein but not mRNA is increased in the Pum2 mutant hippocampus, Glur2 transcripts are increased in mutant polysome fractions, and overexpression of PUM2 led to repression of reporter expression containing the 3'Untranslated Region (3'UTR) of Glur2, suggesting translation of GLUR2 was increased in the absence of Pum2. Overall, these studies provide a molecular mechanism for the increased temporal lobe excitability observed with PUM2 loss and suggest PUM2 might contribute to intractable temporal lobe epilepsy.
Insights
PUMILIO 2 (PUM2) loss increases brain synapse density and glutamate receptor 2 (GLUR2) translation, leading to temporal lobe hyperexcitability and suggesting a role in epilepsy.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- PUMILIO 2 (PUM2) is an RNA-binding protein with conserved roles in development and synaptic function.
- PUM2 deficiency is linked to epileptiform activity and reduced PUM2 levels in epilepsy patients and models.
- The precise in vivo mechanisms by which PUM2 influences synaptic function and seizures remain unclear.
Purpose of the Study:
- To investigate the in vivo role of PUM2 in regulating synaptic function and neuronal excitability.
- To elucidate the molecular mechanisms underlying PUM2's influence on synaptic proteins, particularly glutamate receptors.
- To explore the potential contribution of PUM2 to temporal lobe epilepsy.
Main Methods:
- Analysis of PUM2 expression in the brain, particularly the temporal lobe.
- Phenotypic characterization of PUM2 knockout (Pum2-/-) mice, including assessment of dendrite spine and synapse density.
- Quantification of synaptic protein and mRNA levels (e.g., GLUR2) in Pum2-/- mice.
- Investigation of PUM2's translational regulatory activity using reporter assays with the GLUR2 3'UTR.
Main Results:
- PUM2 is highly expressed in the brain, with notable levels in the temporal lobe.
- Pum2-/- mice exhibit significantly increased pyramidal cell dendrite spine and synapse density.
- Up-regulation of excitatory synaptic proteins, including glutamate receptor 2 (GLUR2), was observed in Pum2-/- mice.
- GLUR2 protein, but not mRNA, increased in the mutant hippocampus, indicating post-transcriptional regulation.
- PUM2 directly represses GLUR2 translation via its 3'UTR.
Conclusions:
- Loss of PUM2 leads to increased excitatory synapse density and GLUR2 translation in the brain.
- These molecular changes provide a mechanism for the observed temporal lobe hyperexcitability in PUM2-deficient mice.
- PUM2 plays a critical role in regulating synaptic function and may be a contributing factor in intractable temporal lobe epilepsy.
Related Concept Videos
01:12Synaptic Signaling
01:09Synaptic Signaling
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
01:28Integration of Synaptic Events
01:29Translational Regulation
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
01:16Repressed Memory