The glutamate receptor-interacting protein family of GluR2-binding proteins is required for long-term synaptic depression expression in cerebellar Purkinje cells.
Glutamate receptor-interacting protein 1 (GRIP1) and GRIP2 are closely related proteins that bind GluR2-containing AMPA receptors and couple them to structural and signaling complexes in neurons. Cerebellar long-term synaptic depression (LTD) is a model system of synaptic plasticity that is expressed by persistent internalization of GluR2-containing AMPA receptors. Here, we show that genetic deletion of both GRIP1 and GRIP2 blocks LTD expression in primary cultures of mouse cerebellar neurons but that single deletion of either isoform allows LTD to occur. In GRIP1/2 double knock-out Purkinje cells, LTD can be fully rescued by a plasmid-driving expression of GRIP1 and partially rescued by a GRIP2 plasmid. These results indicate that the GRIP family comprises an essential molecular component for cerebellar LTD.
Takamiya
Kogo
K
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mao
Lifang
L
Huganir
Richard L
RL
Linden
David J
DJ
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D054731:PDZ Domains / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011689:Purkinje Cells / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; C491309:Grip1 protein, mouse; C485567:Grip2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol