The distribution of the components of the cyclic GMP cycle in retina.

Berger, Sosamma J.; DeVries, Gerald W.; Carter, J.G.; Schulz, Demoy W.; Passonneau, P N; Lowry, Oliver H.; Ferrendelli, James A.

doi:10.1016/s0021-9258(19)85861-1

Cited by 84 publications

(17 citation statements)

References 29 publications

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“…4, Table 1), which amounted to 30% of the total retina activity, thus leaving the remaining 70% in the photoreceptor layer. Notably, that distribution was similar to the distribution of guanylate kinase activity in the dissected retinal layers from other mammalian species reported by Berger et al Calculated from Figures 3 and 4S in reference (27), 71%-78% of guanylate kinase activity in rabbit and monkey retinas was associated with the photoreceptor inner segments and outer nuclear layer, and 22%-29% was associated with the outer plexiform layer. It is therefore possible that the bulk of GMP phosphorylation activity in the inner retina (Fig.…”

Section: Discussionsupporting

confidence: 88%

“…Like PDE6, RetGC activity is exclusively present in photoreceptors (34)(35)(36)(37)(38), whereas GMP phosphorylation occurs in both photoreceptors and the inner retina (ref. (27) and Table 1). Hence, the comparison between the GMP phosphorylation and the cyclase in the entire retina would overestimate the rate of GMP phosphorylation over that of GTP consumption by RetGC.…”

Section: Discussionmentioning

confidence: 98%

“…a The entire RetGC activity is present in photoreceptor layer and is undetectable in the inner retina (27,38).…”

Section: Discussionmentioning

confidence: 99%

“…To avoid potential nonspecific effects of RD3 on a complex enzymatically coupled spectrophotometric assay used in study by Wimberg et al (20), we directly monitored [ 3 H]GMP phosphorylation, combining its conversion to [ 3 H]GDP by guanylate kinase and subsequently to [ 3 H]GTP by nucleoside diphosphokinase, highly active in photoreceptors (27), with a possible contribution from succinyl-CoA synthetase of the Krebs cycle in the mitochondrial matrix (28). The method utilized separation of the [ 3 H]GMP substrate (Fig.…”

Section: Comparison Of Guanylate Kinase and Guanylyl Cyclase Activities In Normal And Rd3/rd3 Mouse Retinasmentioning

confidence: 99%

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Retinal degeneration-3 protein promotes photoreceptor survival by suppressing activation of guanylyl cyclase rather than accelerating GMP recycling

Dizhoor

Peshenko

2021

Journal of Biological Chemistry

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Retinal degeneration-3 protein (RD3) deficiency causes photoreceptor dysfunction and rapid degeneration in the rd3 mouse strain and in human Leber’s congenital amaurosis, a congenital retinal dystrophy that results in early vision loss . However, the mechanisms responsible for photoreceptor death remain unclear. Here, we tested two hypothesized biochemical events that may underlie photoreceptor death: (i) the failure to prevent aberrant activation of retinal guanylyl cyclase (RetGC) by calcium-sensor proteins (GCAPs) versus (ii) the reduction of GMP phosphorylation rate, preventing its recycling to GDP/GTP. We found that GMP converts to GDP/GTP in the photoreceptor fraction of the retina ∼24-fold faster in WT mice and ∼400-fold faster in rd3 mice than GTP conversion to cGMP by RetGC. Adding purified RD3 to the retinal extracts inhibited RetGC 4-fold but did not affect GMP phosphorylation in wildtype or rd3 retinas. RD3-deficient photoreceptors rapidly degenerated in rd3 mice that were reared in constant darkness to prevent light-activated GTP consumption via RetGC and phosphodiesterase 6. In contrast, rd3 degeneration was alleviated by deletion of GCAPs. After 2.5 months, only ∼40% of photoreceptors remained in rd3 / rd3 retinas. Deletion of GCAP1 or GCAP2 alone preserved 68% and 57% of photoreceptors, respectively, whereas deletion of GCAP1 and GCAP2 together preserved 86%. Taken together, our in vitro and in vivo results support the hypothesis that RD3 prevents photoreceptor death primarily by suppressing activation of RetGC by both GCAP1 and GCAP2 but do not support the hypothesis that RD3 plays a significant role in GMP recycling.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 98%

“…a The entire RetGC activity is present in photoreceptor layer and is undetectable in the inner retina (27,38).…”

Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Guanylate Kinase and Guanylyl Cyclase Activities In Normal And Rd3/rd3 Mouse Retinasmentioning

confidence: 99%

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Retinal degeneration-3 protein promotes photoreceptor survival by suppressing activation of guanylyl cyclase rather than accelerating GMP recycling

Dizhoor

Peshenko

2021

Journal of Biological Chemistry

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“…ATP serves as substrate for protein phosphorylations (Hermolin, 1981), supports GTP synthesis by transphosphorylation (Berger et al, 1980 ;Schnetkamp and Daemen, 1981), and is used by the inner segment Na+,K'}-ATPase for maintenance of the light-sensitive dark current . ATP also modulates phosphodiesterase activity (Liebman and Pugh, 1980;Kawamura and Bownds, 1981), possibly through phosphorylation of rhodopsin or some other protein (Hermolin et al, 1982;Sitaramayya and Liebman, 1983).…”

Section: Introductionmentioning

confidence: 99%

Light-induced changes in GTP and ATP in frog rod photoreceptors. Comparison with recovery of dark current and light sensitivity during dark adaptation.

Biernbaum¹,

Bownds²

1985

The Journal of General Physiology

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Light decreases GTP and ATP levels in purified suspensions of physiologically active frog rod outer segments still attached to their inner segment ellipsoids (OS-IS). (a) The GTP decrease is slower in OS-IS (t1/2= 40 s) than in isolated outer segments (hi2 = 7 s), which suggests there is more effective buffering in OS-IS. (b) The GTP decrease becomes detectable only at intensities greater than those required to saturate the photoresponse. As the intensity of a continuous light is increased over 4 log units, GTP levels decrease linearly with log intensity by as much as 60% . GTP is reduced to steady intermediate levels during extended illumination of intermediate intensity. (c) At levels of illumination bleaching >0.003% of the rhodopsin, a decrease in ATP levels becomes detectable. (d) Following a flash, GTP levels fall and-then rise with a recovery time dependent on the intensity of the flash. (e) After both 0.2 and 2% flash bleaches, the recovery of GTP levels parallels the recovery of light sensitivity, which is slower than the recovery of the dark current. This raises the possibility of a link between GTP levels and light sensitivity.

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