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PMID:21172611

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Citation

Kato, AS, Gill, MB, Ho, MT, Yu, H, Tu, Y, Siuda, ER, Wang, H, Qian, YW, Nisenbaum, ES, Tomita, S and Bredt, DS (2010) Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron 68:1082-96

Abstract

Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However, the potential for interactions of these subunits within an AMPA receptor complex is unknown. Here, we find that TARPs γ-4, γ-7, and γ-8, but not γ-2, γ-3, or γ-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With γ-8, resensitization occurs with all GluA subunit combinations; however, γ-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates γ-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, γ-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in γ-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic γ-8-containing AMPA receptors. Thus, γ-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.

Links

PubMed PMC3034222 Online version:10.1016/j.neuron.2010.11.026

Keywords

Animals; Cells, Cultured; HEK293 Cells; Hippocampus/physiology; Humans; Ion Channel Gating/genetics; Ion Channel Gating/physiology; Membrane Proteins/deficiency; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mice, Knockout; Rats; Rats, Wistar; Receptors, AMPA/physiology; Synaptic Potentials/genetics; Synaptic Potentials/physiology

Significance

Annotations

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

MOUSE:CNIH2

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNIH2

located_in

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNIH2

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNIH2

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GRIA2

enables

GO:0004971: AMPA glutamate receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GRIA1

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GRIA1

located_in

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GRIA1

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:GRIA3

enables

GO:0004971: AMPA glutamate receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GRIA4

enables

GO:0004971: AMPA glutamate receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CCG7

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

  • part_of:(UBERON:0001890)

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0001890)

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:CNIH2

located_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0001890)

Seeded From UniProt

complete

MOUSE:CCG8

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CCG8

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CCG8

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CCG4

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GRIA1

enables

GO:0004971: AMPA glutamate receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GRIA1

part_of

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GRIA1

part_of

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GRIA1

part_of

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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