Mg 2+ Sets the Range

Abstract

The concentration of guanosine 3′,5′-monophosphate (cGMP) controls the response to light in the retina. Binding of cGMP to a plasma membrane cation channel maintains a small calcium flux. Light promotes the degradation of cGMP, allowing these cyclic nucleotide-gated channels to close, resulting in hyperpolarization and a fall in intracellular calcium concentration. Production of cGMP is intimately associated with this changing calcium concentration such that when calcium is high, guanylyl cyclase-activating proteins (GCAPs) inhibit guanylate cyclase (GC) activity, and when calcium is low, GCAPs activate GC activity. However, in vitro the responsiveness of GCAPs to calcium is outside the range of calcium concentrations present in the retina. Peshenko and Dizhoor report that the Mg 2+ concentration sets the dynamic range of calcium concentrations over which GCAPs regulate GC activity in assays with recombinant GCAP and outer segment membranes or mouse retina homogenate. Tryptophan fluorescence analysis demonstrated direct binding of Mg 2+ to GCAP-1 and GCAP-2 and showed that Mg 2+ alters the binding affinity and profile of GCAPs for calcium. Thus, GCAPs are calcium sensors whose dynamic range to calcium is set by the concentration of Mg 2+ . Mg 2+ does not change much during retinal signaling; therefore, changes in calcium predominate over the regulation of GCAP activity. I. V. Peshenko, A. M. Dizhoor, Guanylyl cyclase-activating proteins (GCAPs) are Ca 2+ /Mg 2+ sensors: Implications for photoreceptor guanylyl cyclase (RetGC) regulation in mammalian photoreceptors. J. Biol. Chem. 279 , 16903-16906 (2004). [Abstract] [Full Text]