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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

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K4Y5

F

Seeded From UniProt

complete

RAT:LGI1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:LGI1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9R1V7

F

Seeded From UniProt

complete

RAT:LGI1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9R1V6

F

Seeded From UniProt

complete

RAT:LGI1

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:LGI1

involved_in

GO:0050806: positive regulation of synaptic transmission

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADA22

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K4Y5

F

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006063: over expression analysis evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006063: over expression analysis evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0000955)

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0000955)

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0006063: over expression analysis evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:ADA22

located_in

GO:0098978: glutamatergic synapse

ECO:0006063: over expression analysis evidence used in manual assertion

C

  • part_of:(UBERON:0000955)

Seeded From UniProt

complete

MOUSE:ADA22

involved_in

GO:0099645: neurotransmitter receptor localization to postsynaptic specialization membrane

ECO:0006063: over expression analysis evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADA22

involved_in

GO:0099645: neurotransmitter receptor localization to postsynaptic specialization membrane

ECO:0006063: over expression analysis evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADA23

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K4Y5

F

Seeded From UniProt

complete


See also

References

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