HOMER BINDS A NOVEL PROLINE-RICH MOTIF AND LINKS GROUP 1 METABOTROPICGLUTAMATE RECEPTORS WITH IP3 RECEPTORS

Group 1 metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we dem onstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Hom er proteins form a physical tether linking mGluRs with the inositol tr isphosphate receptors (IP3R). A novel proline-rich ''Homer ligand'' (P PXXFr) is identified in group 1 mGluRs and IP3R, and these receptors c oimmunoprecipitate as a complex with Homer from brain. Expression of t he 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.