The hippocampus is a key brain region for memory formation. Metabotropic glutamate type 5 receptors (mGlu5R) are strongly expressed in CA1 pyramidal neurons and fine-tune synaptic plasticity. Accordingly， mGlu5R pharmacological manipulation may represent an attractive therapeutic strategy to manage hippocampal-related neurological disorders. Here， by means of a membrane yeast two-hybrid (MYTH) screening， we identified contactin-associated protein 1 (Caspr1)， a type I transmembrane protein member of the neurexin family， as a new mGlu5R partner. We report that mGlu5R and Caspr1 co-distribute and co-assemble both in heterologous expression systems and in rat brain. Furthermore， down-regulation of Caspr... More
The hippocampus is a key brain region for memory formation. Metabotropic glutamate type 5 receptors (mGlu5R) are strongly expressed in CA1 pyramidal neurons and fine-tune synaptic plasticity. Accordingly， mGlu5R pharmacological manipulation may represent an attractive therapeutic strategy to manage hippocampal-related neurological disorders. Here， by means of a membrane yeast two-hybrid (MYTH) screening， we identified contactin-associated protein 1 (Caspr1)， a type I transmembrane protein member of the neurexin family， as a new mGlu5R partner. We report that mGlu5R and Caspr1 co-distribute and co-assemble both in heterologous expression systems and in rat brain. Furthermore， down-regulation of Caspr1 in rat hippocampal primary cultures decreased mGlu5R-mediated signalling. Finally， silencing Caspr1 expression in the hippocampus impaired the impact of mGlu5R on spatial memory. Our results indicate that Caspr1 plays a pivotal role controlling mGlu5R function in hippocampus-dependent memory formation. Hence， this new protein-protein interaction may represent novel target for neurological disorders affecting hippocampal glutamatergic neurotransmission.
