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Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.

Group I metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich "Homer ligand" (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.

Pubmed ID: 9808459

Authors

  • Tu JC
  • Xiao B
  • Yuan JP
  • Lanahan AA
  • Leoffert K
  • Li M
  • Linden DJ
  • Worley PF

Journal

Neuron

Publication Data

October 4, 1998

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA 10309
  • Agency: NIDA NIH HHS, Id: DA 11742
  • Agency: NIMH NIH HHS, Id: KO2 MH01152

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Calcium
  • Calcium Channels
  • Carrier Proteins
  • Dynamins
  • GTP Phosphohydrolases
  • Gene Expression
  • Genes, Immediate-Early
  • Glutamic Acid
  • Inositol 1,4,5-Trisphosphate Receptors
  • Intracellular Membranes
  • Ligands
  • Molecular Sequence Data
  • Neuropeptides
  • Proline
  • Rats
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Metabotropic Glutamate
  • Time Factors