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Sci. Signal., 22 November 2011
Vol. 4, Issue 200, p. ra78
Linking Activity to Abundance
Many G protein–coupled receptors decrease their signaling output when activated by ligands. However, the calcium-sensing receptor (CaSR), which maintains the serum concentration of calcium within a narrow range, is constantly exposed to calcium, leading Grant et al. to investigate how CaSR-mediated signaling increases in response to increases in the concentration of extracellular calcium. Activation of CaSRs by calcium or other agonists resulted in mobilization of CaSRs to the plasma membrane from a large intracellular pool, thereby enabling increased and sustained CaSR signaling. Mutations in CASR can result in hypocalcemia or hypercalcemia; thus, understanding its regulation could help in the development of drugs to treat these conditions. In addition, this mechanism might regulate the signaling output of other receptors that are also constantly exposed to ligands.
Citation: M. P. Grant, A. Stepanchick, A. Cavanaugh, G. E. Breitwieser, Agonist-Driven Maturation and Plasma Membrane Insertion of Calcium-Sensing Receptors Dynamically Control Signal Amplitude. Sci. Signal.4, ra78 (2011).