Ca2+ and Ca2+-interlocked membrane guanylate cyclase signal modulation of neuronal and cardiovascular signal transduction

Citation: Sharma RK, Baehr W, Makino CL and Duda T (2015) Ca 2+ and Ca 2+-interlocked membrane guanylate cyclase signal modulation of neuronal and cardiovascular signal transduction. The papers in this research topic are focused on the extraordinary tale of cyclic GMP: its recognition as a hormonal second messenger and its subsequent interplay with intracellular calcium where the two together become co-messengers in cellular signal transduction processes. In this emerging theme membrane guanylate cyclases sense intracellular as well as extracellular signals. Four original research and 12 review articles sample the extraordinary progress that has been made in the field. The topic introduces the present status of the field with a figure illustrating that cyclic GMP is generated by two structurally different guanylate cyclases, soluble and the membrane form (Figure 1: Sharma and Duda, 2014). The synthetic machinery and the modes of their operation by which they generate cyclic GMP are entirely different, and so are their physiologically regulated processes. Since many of the membrane guanylate cyclases carry multiple names and all names remain in use, the review also provides a guide to the current nomenclature of the membrane guanylate cyclases (Introductory text Table 1). Then it moves on with a lively historical perspective , replete with unexpected twists and turns. Current research suggests that new developments will continue to follow a tortuous but always exciting path! Guanylate cyclase activating proteins or GCAPs are neuronal calcium sensing proteins that serve as subunits in the ROS-GC complex. The review article by Lim et al. (2014) delves into the molecular mechanism by which GCAPs inhibit GC activity when [Ca 2+ ] i is high and stimulate it when [Ca 2+ ] i is low. As it turns out, GCAP1 has a more subtle use for its myristoyl tail, compared to other, related neuronal calcium sensors. Besides the additional forms of GCAPs that are being discovered (cf. Wen et al., 2014), ROS-GC1 is subject to modulation by other Ca 2+ binding proteins: S100B in retinal cones (reviewed by Sharma et al., 2014) and S100B and neurocalcin δ (NCδ) in spermatozoa (Jankowska et al., 2014). Unlike GCAPs, S100B and NCδ stimulate ROS-GC1 at high [Ca 2+ ] i. Co-expression of S100B and GCAPs with ROS-GC1 in the same cells empowers ROS-GC1 with the ability to operate as a novel, bimodal Ca 2+ switch wherein guanylate cyclase activity is elevated at very high and at very …