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

Neuron. 1998 Oct;21(4):717-26. doi: 10.1016/s0896-6273(00)80589-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Dynamins
  • GTP Phosphohydrolases / genetics
  • Gene Expression
  • Genes, Immediate-Early
  • Glutamic Acid / pharmacology
  • Homer Scaffolding Proteins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Intracellular Membranes / metabolism
  • Ligands
  • Molecular Sequence Data
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Neuropeptides / physiology
  • Proline / genetics*
  • Rats
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Time Factors

Substances

  • Calcium Channels
  • Carrier Proteins
  • Homer Scaffolding Proteins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ligands
  • Neuropeptides
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • Proline
  • GTP Phosphohydrolases
  • Dynamins
  • Calcium

Associated data

  • GENBANK/AF093257
  • GENBANK/AF093258
  • GENBANK/AF093259
  • GENBANK/AF093260
  • GENBANK/AF093261
  • GENBANK/AF093262
  • GENBANK/AF093263
  • GENBANK/AF093264
  • GENBANK/AF093265
  • GENBANK/AF093266
  • GENBANK/AF093267
  • GENBANK/AF093268