Ultrastructural localization of retinal guanylate cyclase in human and monkey retinas
ABSTRACT Immuno-imaging with confocal and electron microscopy revealed the localization of retinal guanylate cyclase (RetGC) in human and monkey retinas. Using an antibody against a peptide derived from human RetGC, RetGC was found predominantly in the photoreceptor layer in these retinas, although a small amount of RetGC was detected in various other retinal cells. In particular, the cone outer segments were more densely labeled with the antibody than the rod outer segments. The RetGC in outer segments was localized exclusively in the membrane-rich domains, and appeared to be associated with the marginal region of the disk membrane and/or the plasma membrane. The connecting cilium and its cytoplasmic extension never showed immunoreactivity with the antibody. The localization of RetGC in photoreceptor cells is discussed from the viewpoint of mechanisms for the recovery of photoreceptors to the dark level.
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ABSTRACT: A sequel to these authors' earlier comprehensive reviews which covered the field of mammalian membrane guanylate cyclase (MGC) from its origin to the year 2010, this article contains 13 sections. The first is historical and covers MGC from the year 1963-1987, summarizing its colorful developmental stages from its passionate pursuit to its consolidation. The second deals with the establishment of its biochemical identity. MGC becomes the transducer of a hormonal signal and founder of the peptide hormone receptor family, and creates the notion that hormone signal transduction is its sole physiological function. The third defines its expansion. The discovery of ROS-GC subfamily is made and it links ROS-GC with the physiology of phototransduction. Sections ROS-GC, a Ca(2+)-Modulated Two Component Transduction System to Migration Patterns and Translations of the GCAP Signals Into Production of Cyclic GMP are Different cover its biochemistry and physiology. The noteworthy events are that augmented by GCAPs, ROS-GC proves to be a transducer of the free Ca(2+) signals generated within neurons; ROS-GC becomes a two-component transduction system and establishes itself as a source of cyclic GMP, the second messenger of phototransduction. Section ROS-GC1 Gene Linked Retinal Dystrophies demonstrates how this knowledge begins to be translated into the diagnosis and providing the molecular definition of retinal dystrophies. Section Controlled By Low and High Levels of [Ca(2+)]i, ROS-GC1 is a Bimodal Transduction Switch discusses a striking property of ROS-GC where it becomes a "[Ca(2+)]i bimodal switch" and transcends its signaling role in other neural processes. In this course, discovery of the first CD-GCAP (Ca(2+)-dependent guanylate cyclase activator), the S100B protein, is made. It extends the role of the ROS-GC transduction system beyond the phototransduction to the signaling processes in the synapse region between photoreceptor and cone ON-bipolar cells; in section Ca(2+)-Modulated Neurocalcin δ ROS-GC1 Transduction System Exists in the Inner Plexiform Layer (IPL) of the Retinal Neurons, discovery of another CD-GCAP, NCδ, is made and its linkage with signaling of the inner plexiform layer neurons is established. Section ROS-GC Linkage With Other Than Vision-Linked Neurons discusses linkage of the ROS-GC transduction system with other sensory transduction processes: Pineal gland, Olfaction and Gustation. In the next, section Evolution of a General Ca(2+)-Interlocked ROS-GC Signal Transduction Concept in Sensory and Sensory-Linked Neurons, a theoretical concept is proposed where "Ca(2+)-interlocked ROS-GC signal transduction" machinery becomes a common signaling component of the sensory and sensory-linked neurons. Closure to the review is brought by the conclusion and future directions.Frontiers in Molecular Neuroscience 07/2014; 7:56.
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ABSTRACT: ROS-GC1 belongs to the Ca(2+)-modulated sub-family of membrane guanylate cyclases. It primarily exists and is linked with signaling of the sensory neurons - sight, smell, taste, and pinealocytes. Exceptionally, it is also present and is Ca(2+)-modulated in t he non-neuronal cells, the sperm cells in the testes, where S100B protein serves as its Ca(2+) sensor. The present report demonstrates the identification of an additional Ca(2+) sensor of ROS-GC1 in the testes, neurocalcin δ. Through mouse molecular genetic models, it compares and quantifies the relative input of the S100B and neurocalcin δ in regulating the Ca(2+) signaling of ROS-GC1 transduction machinery, and via immunochemistry it demonstrates the co-presence of neurocalcin δ and ROS-GC1 in the spermatogenic cells of the testes. The suggestion is that in more ways than one the Ca(2+)-modulated ROS-GC1 transduction system is linked with the testicular function. This non-neuronal transduction system may represent an illustration of the ROS-GC1 expanding role in the trans-signaling of the neural and non-neural systems.Frontiers in Molecular Neuroscience 04/2014; 7:34.
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ABSTRACT: Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP, the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca(2+)-sensing elements. There is a light-induced fall in intracellular Ca(2+). As Ca(2+) dissociates from GCAPs in the 20-200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca(2+) and cyclic GMP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca(2+) sensor protein, S100B, complexes with ROS-GC1 and senses the Ca(2+) signal with a K1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca(2+) is bound. Thus, the ROS-GC system in cones functions as a Ca(2+) bimodal switch; with rising intracellular Ca(2+), its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the "bimodal" operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.Frontiers in Molecular Neuroscience 03/2014; 7:21.