Figure 1.

Activation of mGlu₅ receptors triggers diverse distinct and converging signalling pathways. The group I mGlu receptor family preferentially couples to G_q, leading to activation of the canonical PLC–IP₃–DAG–Ca²⁺ pathway. As reviewed in the text, mGlu₅ receptors promiscuously couple to other G proteins as well as alternate second messengers and kinases via mechanisms that can be independent of Ca²⁺ mobilization. Protein–protein interactions with scaffolding and regulatory proteins (blue ovals) add further diversity: integrating different signalling pathways, directly mediating interactions between mGlu₅ receptors and ion channels such as the NMDA receptor and regulating the activity of the mGlu₅ receptor itself. As an additional level of complexity, the signalling pathways and effectors stimulated by mGlu₅ receptor activation also show considerable cell type dependence.