Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins
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Cerebellar LTD requires activation of PKC and is expressed, at least in part, as postsynaptic AMPA receptor internalization. Recently, it was shown that AMPA receptor internalization requires clathrin-mediated endocytosis and depends upon the carboxy-terminal region of GluR2/3. Phosphorylation of Ser-880 in this region by PKC differentially regulates the binding of the PDZ domain-containing proteins GRIP/ABP and PICK1. Peptides, corresponding to the phosphorylated and dephosphorylated GluR2 carboxy-terminal PDZ binding motif, were perfused in cerebellar Purkinje cells grown in culture. Both the dephospho form (which blocks binding of GRIP/ABP and PICK1) and the phospho form (which selectively blocks PICK1) attenuated LTD induction by glutamate/depolarization pairing, as did antibodies directed against the PDZ domain of PICK1. These findings indicate that expression of cerebellar LTD requires PKC-regulated interactions between the carboxy-terminal of GluR2/3 and PDZ domain-containing proteins.
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PICK1 via its BAR-domain can either promote invagination of the plasma membrane or direct GluA2 to regions of invagination where clathrin-mediated endocytosis occurs.
“Via its BAR-domain, PICK1 can either promote the invagination of the plasma membrane or direct GluA2 to regions of invagination where clathrin-mediated endocytosis occurs (Xia et al., 2000, Fiuza et al., 2017).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Xia et al., 2000
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- Authors
- Xia, J., Chung, H. J., Wihler, C., Huganir, R. L., & Linden, D. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Corresponding author
- Linden, David J
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 28
- Issue
- 2
- Pages
- 499-510
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2023426126
- Cited by
- 383
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 2 · 2018: 11 · 2017: 8 · 2016: 12 · 2015: 15 · 2014: 12 · 2013: 16 · 2012: 14
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institute of Mental Health (MH-01590, MH 51106)
- National Institute of Neurological Disorders and Stroke (NS36715, R01NS036715)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- cerebellar long-term depression, protein kinase C, GluR2/3, AMPA receptor internalization, clathrin-mediated endocytosis, PDZ domain proteins, PICK1, Purkinje cells, postsynaptic plasticity
- MeSH terms
- Animals, Antibodies, Binding, Competitive, Calcium, Carrier Proteins, Cells, Cultured, Cerebellum, Nerve Tissue Proteins, Neural Inhibition, Neuronal Plasticity, Nuclear Proteins, Peptide Fragments, Phosphorylation, Protein Kinase C, Purkinje Cells, Recombinant Fusion Proteins, Time, Protein Structure, Tertiary, Receptors, AMPA, Patch-Clamp Techniques, Cell Cycle Proteins, Excitatory Postsynaptic Potentials, Amino Acid Motifs, Adaptor Proteins, Signal Transducing, Mice
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