HOMER REGULATES THE ASSOCIATION OF GROUP 1 METABOTROPIC GLUTAMATE RECEPTORS WITH MULTIVALENT COMPLEXES OF HOMER-RELATED, SYNAPTIC PROTEINS

Homer is a neuronal immediate early gene (IEG) that is enriched at exc itatory synapses and binds group 1 metabotropic glutamate receptors (m GluRs). Here, we characterize a family of Homer-related proteins deriv ed from three distinct genes. Like Homer IEG (now termed Homer 1a), al l new members bind group 1 mGluRs. In contrast to Homer 1a, new member s are constitutively expressed and encode a C-terminal coiled-coil (CC ) domain that mediates self-multimerization. CC-Horners form natural c omplexes that cross-link mGluRs and are enriched at the postsynaptic d ensity. Homer 1a does not multimerize and blocks the association of mG luRs with CC-Homer complexes. These observations support a model in wh ich the dynamic expression of Homer 1a competes with constitutively ex pressed CC-Homers to modify synaptic mGluR properties.