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PMID:16990550
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| Citation |
Fukata, Y, Adesnik, H, Iwanaga, T, Bredt, DS, Nicoll, RA and Fukata, M (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792-5 |
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| Abstract |
Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations in ion channels. However, one form of epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We show that ADAM22, a transmembrane protein that when mutated itself causes seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 fails to bind to ADAM22. ADAM22 is anchored to the postsynaptic density by cytoskeletal scaffolds containing stargazin. These studies in rat brain indicate possible avenues for understanding human epilepsy. |
| Links |
PubMed Online version:10.1126/science.1129947 |
| Keywords |
ADAM Proteins/chemistry; ADAM Proteins/genetics; ADAM Proteins/metabolism; Animals; Calcium Channels/metabolism; Cell Line; Cerebellar Cortex/metabolism; Cerebral Cortex/metabolism; Epilepsies, Partial/physiopathology; Hippocampus/metabolism; Hippocampus/physiology; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Ligands; Membrane Proteins/metabolism; Mice; N-Methylaspartate/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Protein Binding; Protein Structure, Tertiary; Proteins/metabolism; Rats; Receptors, AMPA/metabolism; Recombinant Fusion Proteins/metabolism; Synapses/metabolism; Synaptic Transmission; Transfection; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism |
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