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Front Mol Neurosci. 2012 Apr 9;5:44. doi: 10.3389/fnmol.2012.00044. eCollection 2012.

Antithetical modes of and the Ca(2+) sensors targeting in ANF-RGC and ROS-GC1 membrane guanylate cyclases.

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  • 1Research Divisions of Biochemistry and Molecular Biology, The Unit of Regulatory and Molecular Biology, Salus University, Elkins Park PA, USA.


THE MEMBRANE GUANYLATE CYCLASE FAMILY HAS BEEN BRANCHED INTO THREE SUBFAMILIES: natriuretic peptide hormone surface receptors, Ca(2+)-modulated neuronal ROS-GC, and Ca(2+)-modulated odorant surface receptor ONE-GC. The first subfamily is solely modulated by the extracellularly generated hormonal signals; the second, by the intracellularly generated sensory and sensory-linked signals; and the third, by combination of these two. The present study defines a new paradigm and a new mechanism of Ca(2+) signaling. (1) It demonstrates for the first time that ANF-RGC, the prototype member of the surface receptor subfamily, is stimulated by free [Ca(2+)](i). The stimulation occurs via myristoylated form of neurocalcin δ, and both the guanylate cyclase and the calcium sensor neurocalcin δ are present in the glomerulosa region of the adrenal gland. (2) The EF-2, EF-3 and EF-4 hands of GCAP1 sense the progressive increment of [Ca(2+)](i) and with a K(1/2) of 100 nM turn ROS-GC1 "OFF." In total reversal, the same EF hands upon sensing the progressive increment of [Ca(2+)](i) with K(1/2) turn ONE-GC "ON." The findings suggest a universal Ca(2+)-modulated signal transduction theme of the membrane guanylate cyclase family; demonstrate that signaling of ANF-RGC occurs by the peptide hormones and also by [Ca(2+)](i) signals; that for the Ca(2+) signal transduction, ANF-RGC functions as a two-component transduction system consisting of the Ca(2+) sensor neurocalcin δ and the transducer ANF-RGC; and that the neurocalcin δ in this case expands beyond its NCS family. Furthermore, the study shows a novel mechanism of the [Ca(2+)](i) sensor GCAP1 where it acts as an antithetical NCS for the signaling mechanisms of ROS-GC1 and ONE-GC.


GCAP1; atrial natriuretic factor receptor membrane guanylate cyclase; calcium; cyclic GMP; membrane guanylate cyclase; neurocalcin δ; neuronal calcium sensors; olfactory neuroepithelium membrane guanylate cyclase

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