The Glutamate Receptor-Interacting Protein Family of GluR2-Binding Proteins Is Required for Long-Term Synaptic Depression Expression in Cerebellar Purkinje Cells
Copyright policy )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.
- Johns Hopkins University United States
- University of California, San Francisco United States
- Johns Hopkins Medicine United States
- Howard Hughes Medical Institute United States
- Johns Hopkins University School of Medicine United States
Patch-Clamp Techniques, Long-Term Synaptic Depression, Green Fluorescent Proteins, Intracellular Signaling Peptides and Proteins, Glutamic Acid, PDZ Domains, Mice, Transgenic, Nerve Tissue Proteins, Embryo, Mammalian, Electric Stimulation, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Mice, Cerebellum, Mutation, Excitatory Amino Acid Agonists, Animals, Carrier Proteins, Cells, Cultured, Adaptor Proteins, Signal Transducing
Patch-Clamp Techniques, Long-Term Synaptic Depression, Green Fluorescent Proteins, Intracellular Signaling Peptides and Proteins, Glutamic Acid, PDZ Domains, Mice, Transgenic, Nerve Tissue Proteins, Embryo, Mammalian, Electric Stimulation, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Mice, Cerebellum, Mutation, Excitatory Amino Acid Agonists, Animals, Carrier Proteins, Cells, Cultured, Adaptor Proteins, Signal Transducing
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