Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins

Jun Xia, Hee Jung Chung, Cornelia Wihler, Richard L. Huganir, David J. Linden

Research output: Contribution to journalArticlepeer-review

313 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)499-510
Number of pages12
JournalNeuron
Volume28
Issue number2
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins'. Together they form a unique fingerprint.

Cite this