PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression.
AMPAR (α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an ion channel involved in the formation of synaptic plasticity. However, the molecular mechanism that couples plasticity stimuli to the trafficking of postsynaptic AMPAR remains poorly understood. Here, we show that PIKE (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by promoting GluA2/GRIP1 association. PIKE-L ... directly interacts with both GluA2 and GRIP1 and forms a tertiary complex upon glycine-induced NMDA receptor activation. PIKE-L is also essential for glycine-induced GluA2-associated PI3K activation. Genetic ablation of PIKE (PIKE(-/-)) in neurons suppresses GluA2-associated PI3K activation, therefore inhibiting the subsequent surface expression of GluA2 and the formation of long-term potentiation. Our findings suggest that PIKE-L is a critical factor in controlling synaptic AMPAR insertion.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Brain, Carrier Proteins, Cells, Cultured, GTP Phosphohydrolases, GTP-Binding Proteins, GTPase-Activating Proteins, Glycine, HEK293 Cells, Humans, Long-Term Potentiation, Mice, Monomeric GTP-Binding Proteins, Nerve Tissue Proteins, Neurons, Phosphatidylinositol 3-Kinases, Rats, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate
Adaptor Proteins, Signal Transducing, Animals, Brain, Carrier Proteins, Cells, Cultured, GTP Phosphohydrolases, GTP-Binding Proteins, GTPase-Activating Proteins, Glycine, HEK293 Cells, Humans, Long-Term Potentiation, Mice, Monomeric GTP-Binding Proteins, Nerve Tissue Proteins, Neurons, Phosphatidylinositol 3-Kinases, Rats, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate
EMBO J.
Date: Aug. 16, 2011
PubMed ID: 21847098
View in: Pubmed Google Scholar
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