Regulation of Metabotropic Glutamate Receptor Signaling by the Post-Synaptic Scaffold Homer
Group I mGluRs (mGluRs 1&5) are the predominant mGluRs expressed near the post-synaptic density at glutamatergic synapses. These receptors are anchored near the PSD by the post-synaptic scaffolding proteins called Homer. Work in the Kammermeier lab has been among the first to show that Homer association can act as a molecular switch for group I mGluR signaling, uncoupling mGluR1&5 from a large set of effectors in the absence of Homer scaffolds (voltage gated ion channels expressed extrasynaptically) to a separate set of effectors located near the PSD (ligand gated glutamate receptors, IP3 receptors, and DAG lipases). In addition, we showed that endogenous Homer protein expression was sufficient to strongly alter mGluR-effector coupling in neurons. More recent work with collaborator Paul Worley at Johns Hopkins University has focused on the adaptor protein Preso1, which can dynamically enhance phosphorylation of the Homer binding site on mGluRs to more effectively change coupling to various effectors downstream of receipts activity.