adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway

Definition

Target type: biologicalprocess

An adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway initiated by glutamate binding to its receptor, and ending with the regulation of a downstream cellular process. [GOC:dph, GOC:mah, GOC:signaling, GOC:tb]

The adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway is a complex process involving multiple steps:

1. **Glutamate Binding:** The pathway begins with the binding of glutamate, an excitatory neurotransmitter, to its specific receptor, a G protein-coupled receptor (GPCR) known as the metabotropic glutamate receptor (mGluR). These receptors are classified into three groups (Group I, II, and III), with Group II and III mGluRs primarily involved in this pathway.

2. **G Protein Activation:** Upon glutamate binding, the mGluR undergoes a conformational change, activating a heterotrimeric G protein (Gi/o). This protein is composed of three subunits: α, β, and γ. The α subunit is bound to GDP in its inactive state.

3. **GDP-GTP Exchange:** The activated mGluR promotes the exchange of GDP for GTP on the α subunit of the G protein. This exchange triggers the dissociation of the α subunit from the βγ dimer, rendering both components active.

4. **Adenylate Cyclase Inhibition:** The activated α subunit (αi/o) directly interacts with and inhibits adenylate cyclase, an enzyme responsible for converting ATP into cyclic AMP (cAMP). The inhibition of adenylate cyclase leads to a decrease in intracellular cAMP levels.

5. **Downstream Signaling:** Reduced cAMP levels impact various downstream signaling pathways. This includes the modulation of ion channel activity, protein kinase activity, and gene expression. For example, decreased cAMP can suppress the activity of protein kinase A (PKA), a key regulator of many cellular processes.

6. **Termination:** The signaling cascade is ultimately terminated by the hydrolysis of GTP to GDP on the α subunit of the G protein. This allows the α subunit to reassociate with the βγ dimer, restoring the inactive G protein.

Overall, this pathway plays a crucial role in modulating neuronal excitability, synaptic plasticity, and various cognitive functions. The inhibition of adenylate cyclase by the Gi/o protein ultimately leads to a reduction in intracellular cAMP levels, resulting in a dampening of neuronal signaling.'
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Proteins (9)

Compounds (94)