HOMER - A PROTEIN THAT SELECTIVELY BINDS METABOTROPIC GLUTAMATE RECEPTORS

Spatial localization and clustering of membrane proteins is critical t o neuronal development and synaptic plasticity. Recent studies have id entified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors( 1) and ion channels(2). PDZ proteins are thought to have a role in def ining the cellular distribution of the proteins that interact with the m, Here we report a novel dendritic protein, Homer, that contains a si ngle, PDZ-like domain and binds specifically to the carboxy terminus o f phosphoinositide-linked metabotropic glutamate receptors. Homer is h ighly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ famil y in that its expression is regulated as an immediate early gene and i s dynamically responsive to physiological synaptic activity, particula rly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.