Disrupting GluA2-GAPDH Interaction Affects Axon and Dendrite Development
| Autor: | Ping Su, Kyle Ethan Wang, Frankie H. F. Lee, Qi Wan, Fang Liu, Yu-Feng Xie |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Dendritic spine Dendritic Spines Neurogenesis Growth Cones Cell Count Nerve Tissue Proteins Receptors Cell Surface Dendrite AMPA receptor Biology Hippocampal formation Article Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Amino Acid Sequence Receptors AMPA Axon Growth cone Cells Cultured Cell Proliferation Multidisciplinary Lysine Brain Glyceraldehyde-3-Phosphate Dehydrogenases Acetylation Long-term potentiation Dendrites Anatomy Embryo Mammalian Axons Peptide Fragments Cell biology 030104 developmental biology medicine.anatomical_structure Animals Newborn nervous system Synapses Calcium Channels Neuron Peptides 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep30458 |
| Popis: | GluA2-containing AMPA receptors (AMPARs) play a critical role in various aspects of neurodevelopment. However, the molecular mechanisms underlying these processes are largely unknown. We report here that the interaction between GluA2 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is necessary for neuron and cortical development. Using an interfering peptide (GluA2-G-Gpep) that specifically disrupts this interaction, we found that primary neuron cultures with peptide treatment displayed growth cone development deficits, impairment of axon formation, less dendritic arborization and lower spine protrusion density. Consistently, in vivo data with mouse brains from pregnant dams injected with GluA2-G-Gpep daily during embryonic day 8 to 19 revealed a reduction of cortical tract axon integrity and neuronal density in post-natal day 1 offspring. Disruption of GluA2-GAPDH interaction also impairs the GluA2-Plexin A4 interaction and reduces p53 acetylation in mice, both of which are possible mechanisms leading to the observed neurodevelopmental abnormalities. Furthermore, electrophysiological experiments indicate altered long-term potentiation (LTP) in hippocampal slices of offspring mice. Our results provide novel evidence that AMPARs, specifically the GluA2 subunit via its interaction with GAPDH, play a critical role in cortical neurodevelopment. |
| Databáze: | OpenAIRE |
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