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