Localization of the Cyclic ADP-Ribose-Dependent Calcium Signaling Pathway in Bovine Rod Outer Segments

Panfoli, Isabella; Ravera, Silvia; Fabiano, Andrea; Magrassi, Raffaella; Diaspro, Alberto; Morelli, Alessandro; Pepe, I.M.

doi:10.1167/iovs.06-0543

Cited by 9 publications

(16 citation statements)

References 56 publications

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“…Indeed, it is conceivable that the observed rise in retinal Ca 2+ levels [145] is only secondary to the degeneration process and it is not even clear whether it occurs in photoreceptors or in other retinal cell types such as Müller glial cells [153]. Furthermore, fluctuations in cytosolic Ca 2+ may be caused not only by Ca 2+ influx from extracellular sources but also by intracellular release from either the mitochondria, photoreceptor discs, or the endoplasmatic reticulum (ER) [148,154].…”

Section: Role Of Calcium Energetic Status and The Endoplasmatic Retmentioning

confidence: 99%

Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

et al. 2008

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Photoreceptor cell death is the major hallmark of a group of human inherited retinal degenerations commonly referred to as retinitis pigmentosa (RP). Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Previous research work has focused on apoptosis, but recent evidence suggests that photoreceptor cell death may result primarily from non-apoptotic mechanisms independently of AP1 or p53 transcription factor activity, Bcl proteins, caspases, or cytochrome c release. This review briefly describes some animal models used for studies of retinal degeneration, with particular focus on the rd1 mouse. After outlining the major features of different cell death mechanisms in general, we then compare them with results obtained in retinal degeneration models, where photoreceptor cell death appears to be governed by, among other things, changes in cyclic nucleotide metabolism, downregulation of the transcription factor CREB, and excessive activation of calpain and PARP. Based on recent experimental evidence, we propose a putative non-apoptotic molecular pathway for photoreceptor cell death in the rd1 retina. The notion that inherited photoreceptor cell death is driven by non-apoptotic mechanisms may provide new ideas for future treatment of RP.

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Section: Role Of Calcium Energetic Status and The Endoplasmatic Retmentioning

confidence: 99%

Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

et al. 2008

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“…Conversely, cADPR, a known physiological activator of ryanodine receptor (RyR) channels, evoked Ca 2+ release from suspensions of osmotically intact disks prepared from bovine ROS; ADPR cyclase activity was detected in disk, but not cytosolic ROS fraction [20]. Finally, isolated disks contain a protein with high molecular weight similar to RyRs (~520 kDa; [119]) whereas RyR1 was localized to the disk rim using antibody staining and electron microscopy [87]. Taken together, these findings suggest that rod disks express the typical ER-like Ca 2+ signaling arrangement possibly associated with SERCA3 and RyR1 [51, 87].…”

Section: The Outer Segmentmentioning

confidence: 99%

Calcium Stores in Vertebrate Photoreceptors

Križaj

2012

Advances in Experimental Medicine and Biology

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This review lays out the emerging evidence for the fundamental role of Ca2+ stores and store-operated channels in the Ca2+ homeostasis of rods and cones. Calcium-induced calcium release (CICR) is a major contributor to steady-state and light-evoked photoreceptor Ca2+ homeostasis in the darkness whereas store-operated Ca2+ channels play a more significant role under sustained illumination conditions. The homeostatic response includes dynamic interactions between the plasma membrane, endoplasmic reticulum (ER), mitochondria and/or outer segment disk organelles which dynamically sequester, accumulate and release Ca2+. Coordinated activation of SERCA transporters, ryanodine receptors (RyR), inositol triphosphate receptors (IP3Rs) and TRPC channels amplifies cytosolic voltage-operated signals but also provides a memory trace of previous exposures to light. Store-operated channels, activated by the STIM1 sensor, prevent pathological decrease in [Ca2+]i mediated by excessive activation of PMCA transporters in saturating light. CICR and SOCE may also modulate the transmission of afferent and efferent signals in the outer retina. Thus, Ca2+ stores provide additional complexity, adaptability, tuneability and speed to photoreceptor signaling.

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“…The technique described is an improvement of a protocol that we utilized to demonstrate the presence of ryanodine receptors ͑RyR s ͒ on the rod disk. 15 In the cited paper large aggregates were present. The object shown in the orthogonal projection ͓Fig.…”

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confidence: 95%

Confocal laser scanning microscopy of retinal rod outer segment intact disks: new labeling technique

et al. 2007

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Abstract. Vertebrate retinal rod outer segment disks house the proteins involved in the phototransduction cascade that converts light into neuronal signal. We develop a technique for the immunofluorescent labeling of osmotically intact isolated rod outer segment disks for confocal laser scanning microscopy imaging. Osmotically intact Ficoll-flotation isolated bovine disks are directly labeled with antibodies in solution. For the first time, osmotically intact single disks can be visualized. Thus, imaging of purified disks, based on advanced optical techniques, may serve as a powerful complement to other methods in studies on phototransduction. In fact, even though much is known about the rod outer segment photoresponse, some unanswered questions remain, particularly about ATP supply, light adaptation, and morphogenesis. Oct. 3, 2007. Confocal laser scanning microscopy ͑CLSM͒ is a valuable tool for obtaining high-resolution images and 3-D reconstructions. 1 Vertebrate rod photoreceptors, the neurons responsible for visual phototransduction, mediate vision at low-light intensities using a modified cilium ͑called the outer segment͒ for the detection of light. The rod outer segment ͑rod OS͒ is packed with hundreds of membrane sacs, called disks, on the surface of which the initial biochemical reactions of visual transduction take place. 2,3 The disks, with dimensions of about 1 m diam, 4,5 are regularly stacked on top of each other with a repeat distance of 300 Å. 4 The visual pigment rhodopsin ͑Rh͒, an integral membrane protein, accounts for about 90% 6 of total disk protein content. Photoreceptor disks are continuously renewed through formation of new disks at the base of the outer segment, displaced distally along the length of the outer segment, and eventual detachment and phagocytosis occurs by adjacent pigment epithelial cells. 7 Several microscopy techniques have been used to analyze the morphological organization of rods and to identify the membrane proteins in rod OS. For example, measurements of the ellipsoid mitochondria density, sizes, and shapes of inner segments were conducted by electron microscopy and Nomads differential interference contrast ͑NDIC͒ imaging. 8 Studies on the stability of Rh in native membranes were done by single-molecule force spectroscopy. 9 Moreover, a recent progress in modeling the native conformation of Rh was based on topography of the disk membranes recorded by an atomic force microscope ͑AFM͒. 9 CLSM was only used on whole retina or rod OS to observe the protein distribution in the disk incisures. 10 Therefore, even though rod imaging has been achieved in many ways, to the best of our knowledge, until now no study has been reported regarding the application of immunofluorescence for confocal optical imaging of isolated intact disks. In fact, even though fluorescent optical imaging is among the most widely used approach for studying cells in vivo, it is not easily applicable for subcellular fractions. Apart from the classic inclusion methods, it is difficult to isolate an...

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Localization of the Cyclic ADP-Ribose-Dependent Calcium Signaling Pathway in Bovine Rod Outer Segments

Abstract: A cADPR metabolism may be present in retinal ROS discs, which may be Ca(2+) stores operated by cADPR. A model is proposed for the physiological role of cADPR-mediated Ca(2+) release in bovine ROS.

Cited by 9 publications

References 56 publications

Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

Calcium Stores in Vertebrate Photoreceptors

Confocal laser scanning microscopy of retinal rod outer segment intact disks: new labeling technique

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