Gq-coupled receptors activate cAMP signaling to regulate brain synapses

By studying G protein–coupled receptors (GPCRs) in mouse hippocampal slices, Qi Ding and colleagues provide evidence of unconventional receptor signaling that has implications for the function of synapses in the brain. When bound by their ligands outside of cells, GPCRs activate distinct signaling pathways that depend on which G proteins they couple to. GPCRs that couple to G_s or G_i proteins respectively stimulate or inhibit enzymes called adenylyl cyclases (ADCYs). These interactions lead to either increased or decreased amounts of a signaling molecule called cAMP.

Meanwhile, GPCRs that couple to G_q proteins activate phospholipase enzymes to generate intracellular calcium ions (Ca²⁺). Ding et al. took slices of the hippocampus from mouse brains and measured responses to the stimulation of muscarinic acetylcholine receptors or metabotropic glutamate receptors that couple to G_q proteins. They found that the stimulation of these receptors led to the expected increases in Ca²⁺, and that cAMP abundance and signaling also rose.

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American Association for the Advancement of Science (AAAS)

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