Functional Comparison of Rod and Cone Gαt on the Regulation of Light Sensitivity*

Mao, Wen; Miyagishima, Kiyoharu; Yao, Yifan; Soreghan, Brian A.; Sampath, Alapakkam P.; Chen, Jeannie

doi:10.1074/jbc.m112.430058

Cited by 19 publications

(22 citation statements)

References 65 publications

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“…Second, down-regulation of PDE␣␤ catalytic subunits was also observed in two different transgenic mouse lines that express either a GTP hydrolysis-deficient human cone transducin (45) or mouse rod transducin (46), suggesting that the mutant transducin, locked in the active conformation, sequestered mouse rod PDE6␥, leading to structural instability and degradation of PDE␣␤. The ability of cone transducin to bind rod PDE6␥ is supported by our recent study demonstrating that mouse cone transducin activated rod PDE6 with similar efficiency (47). Normal retinal morphology in the GTP hydrolysisdeficient transducin mutant mice indicates that PDE instability alone does not trigger cell death.…”

Section: Our Findings On Arr1supporting

confidence: 58%

Induction of the Unfolded Protein Response by Constitutive G-protein Signaling in Rod Photoreceptor Cells

Chen

2014

Journal of Biological Chemistry

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Background: Excessive light exposure and genetic mutations that act as "equivalent light" cause photoreceptor cell death. Results: Prolonged transducin signaling, but not channel closure, induces endoplasmic reticulum stress. Conclusion: Induction of UPR is a distinct cell death pathway caused by transducin signaling. Significance: Manipulation of UPR may prolong photoreceptor cell survival in transducin-induced retinal light damage.

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Section: Our Findings On Arr1supporting

confidence: 58%

Induction of the Unfolded Protein Response by Constitutive G-protein Signaling in Rod Photoreceptor Cells

Chen

2014

Journal of Biological Chemistry

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“…In control mice (Atg5 f/+ ;cre + ), Tα levels decreased when the mice are exposed to light in relation to the levels observed after dark-adaptation (Figure 8a), confirming published observations. 48,49 However, in the Atg5 ΔRod retina, Tα levels did not vary between light and dark conditions suggesting that Atg5 is necessary to reduce the level of rod transducin in the light-exposed retinae. Quantification of data from four separate experiments is presented in Figure 8b confirmed these findings.…”

Section: Rod Degeneration In Atg5mentioning

confidence: 91%

“…It is known that level of transducin is optimal during dark adaptation and that light exposure reduces its levels. 48,49 Therefore, we asked whether the light-induced reduction in transducin might be related to autophagic degradation by measuring the level of Tα in darkadapted and light-adapted retinae from control and Atg5 ΔRod mice. In control mice (Atg5 f/+ ;cre + ), Tα levels decreased when the mice are exposed to light in relation to the levels observed after dark-adaptation (Figure 8a), confirming published observations.…”

Section: Rod Degeneration In Atg5mentioning

confidence: 99%

Autophagy supports survival and phototransduction protein levels in rod photoreceptors

et al. 2015

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Damage and loss of the postmitotic photoreceptors is a leading cause of blindness in many diseases of the eye. Although the mechanisms of photoreceptor death have been extensively studied, few studies have addressed mechanisms that help sustain these non-replicating neurons for the life of an organism. Autophagy is an intracellular pathway where cytoplasmic constituents are delivered to the lysosomal pathway for degradation. It is not only a major pathway activated in response to cellular stress, but is also important for cytoplasmic turnover and to supply the structural and energy needs of cells. We examined the importance of autophagy in photoreceptors by deleting the essential autophagy gene Atg5 specifically in rods. Loss of autophagy led to progressive degeneration of rod photoreceptors beginning at 8 weeks of age such that by 44 weeks few rods remained. Cone photoreceptor numbers were only slightly diminished following rod degeneration but their function was significantly decreased. Rod cell death was apoptotic but was not dependent on daily light exposure or accelerated by intense light. Although the light-regulated translocation of the phototransduction proteins arrestin and transducin were unaffected in rods lacking autophagy, Atg5-deficient rods accumulated transducin-α as they degenerated suggesting autophagy might regulate the level of this protein.This was confirmed when the light-induced decrease in transducin was abolished in Atg5-deficient rods and the inhibition of autophagy in retinal explants cultures prevented its degradation. These results demonstrate that basal autophagy is essential to the long-term health of rod photoreceptors and a critical process for maintaining optimal levels of the phototransduction protein transducin-α. As the lack of autophagy is associated with retinal degeneration and altered phototransduction protein degradation in the absence of harmful gene products, this process may be a viable therapeutic target where rod cell loss is the primary pathologic event. Autophagy is an intracellular pathway where cytoplasmic constituents are delivered to the lysosomes for degradation. Defective autophagy can contribute to the age-dependent accumulation of damaged proteins and organelles leading to altered cellular homeostasis and loss of function. [1][2][3][4][5] The metabolic roles of autophagy can be classified into two types, basal and induced. In nutrient-rich conditions, autophagy is suppressed but still occurs at low levels (basal autophagy); however, when cells are subjected to stress (starvation, injury, hypoxia), autophagy is activated immediately (induced autophagy). 6 Induced autophagy maintains the amino acid pool inside cells to adapt to starvation while constitutive autophagy has been shown to function as a cell-repair mechanism that is important for long-lived postmitotic cells. 7-11 Defects in autophagy have been associated with neurodegenerative diseases, 12-15 diabetes, 16,17 lysosomal storage disease 18 and the loss of vision. 19 In addition to macroautophagy, m...

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“…Mao and colleagues () then did a similar experiment also using a transgenic approach but with a different result. Rods in their mice expressed less cone Tα than GNAT2C rods and were less sensitive than WT rods, but the decrease in sensitivity seemed to depend only upon the expression level of the transducin and not upon the properties of cone Tα.…”

Section: Introductionmentioning

confidence: 99%

Why are rods more sensitive than cones?

Ingram

Sampath

Fain

2016

The Journal of Physiology

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105

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Cone RodPhotopigment:Cone Rh Rod Rh G protein (transducin):Phosphodiesterase:cGMP-gated channels: A3+B3 A1+B1Lower GAP expression have a different anatomy, with only rods containing membranous discs enclosed by the plasma membrane. These differences must be responsible for the difference in absolute sensitivity, but which are essential? Recent research particularly expressing cone proteins in rods or changing the level of expression seem to show that many of the molecular differences in the activation and decay of the response may have each made a small contribution as evolution proceeded stepwise with incremental increases in sensitivity. Rod outer-segment discs were not essential and developed after single-photon detection. These experiments collectively provide a new understanding of the two kinds of photoreceptors and help to explain how gene duplication and the formation of rod-specific proteins produced the duplex retina, which has remained remarkably constant in physiology from amphibians to man. Abstract figure legend Rods evolved from cones or their progenitors through the emergence of distinct isoforms and altered expression levels of proteins required for transducing light into an electrical signal. These changes must collectively explain why rods are more sensitive.

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Functional Comparison of Rod and Cone Gαt on the Regulation of Light Sensitivity*

Cited by 19 publications

References 65 publications

Induction of the Unfolded Protein Response by Constitutive G-protein Signaling in Rod Photoreceptor Cells

Induction of the Unfolded Protein Response by Constitutive G-protein Signaling in Rod Photoreceptor Cells

Autophagy supports survival and phototransduction protein levels in rod photoreceptors

Why are rods more sensitive than cones?

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