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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
IRSp53 accumulates at the postsynaptic density under excitatory conditions
Ayse Dosemeci1, Amelia Burch1, Hannah Loo1
1Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
Insulin receptor substrate p53 (IRSp53) accumulates at the postsynaptic density (PSD) in neurons upon stimulation. This accumulation suggests a structural role for IRSp53 in organizing synaptic scaffolds and the actin cytoskeleton.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Insulin receptor substrate p53 (IRSp53) is a key protein found at the postsynaptic density (PSD).
- IRSp53 interacts with major PSD scaffolds like PSD-95 and Shanks, and also with F-actin.
Purpose of the Study:
- To investigate the distribution and dynamics of IRSp53 at the PSD in cultured hippocampal neurons.
- To determine how neuronal excitation affects IRSp53 localization within the PSD.
Main Methods:
- Immuno-electron microscopy was employed to visualize IRSp53 distribution.
- Cultured hippocampal neurons were subjected to depolarization (high K+) and NMDA receptor activation.
Main Results:
- IRSp53 labeling was concentrated at the PSD under basal conditions.
- Neuronal depolarization with high K+ increased IRSp53 PSD intensity by 36%.
- NMDA receptor activation increased IRSp53 PSD intensity by 53%, with accumulation in the deeper PSD region (pallium).
Conclusions:
- IRSp53 accumulation in the deeper PSD pallium under stimulation suggests a role beyond effector function for membrane-bound GTPases.
- These findings indicate a potential structural role for IRSp53 in organizing Shank scaffolds and linking the PSD to the actin cytoskeleton.
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