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

Chen, Jeannie

doi:10.1074/jbc.m114.595207

Cited by 23 publications

(27 citation statements)

References 54 publications

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“…As expected, the GCAP2 signal was not observed in Gcap2 -/-or Gcaps -/-cones ( Fig. 1 bottom two panels), thereby confirming the specificity of the GCAP2 antibody (33). Together, these results clearly demonstrate that GCAP2 is expressed in mouse cones.…”

Section: Gcap2supporting

confidence: 71%

Guanylate cyclase–activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors

Vinberg

Peshenko

Chen

et al. 2018

Journal of Biological Chemistry

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Section: Gcap2supporting

confidence: 71%

Guanylate cyclase–activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors

Vinberg

Peshenko

Chen

et al. 2018

Journal of Biological Chemistry

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“…Moreover, the G90D mutation actually rescues the retinal degeneration induced by a mutation in the guanylate cyclase activating protein, GCAP-1, which leads to elevated levels of cGMP (Woodruff et al, 2007). Interestingly, a study of effects of phototransduction cascade mutants found evidence that constitutive G-protein activation due to inactivating mutations in rhodopsin kinase or arrestin, but not constitutive membrane hyperpolarization due to inactivation of the cGMP-gated cation channel that is the ultimate downstream target of the phototransduction cascade, led to activation of the Unfolded Protein Response (Wang and Chen, 2014). Thus, constitutive signaling may act on cell survival differently, depending on the step(s) of the cascade affected.…”

Section: Rod Dystrophiesmentioning

confidence: 99%

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Wensel

Zhang

Anastassov

et al. 2016

Progress in Retinal and Eye Research

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The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural features of the rod and the metabolic processes required for highly amplified light detection seem to have rendered the rod especially sensitive to structural and metabolic defects, so that a large number of gene defects are primarily associated with rod cell death and give rise to blinding retinal dystrophies. The structures of the rod, especially those of the sensory cilium known as the outer segment, have been the subject of structural, biochemical, and genetic analysis for many years, but the molecular bases for rod morphogenesis and for cell death in rod dystrophies are still poorly understood. Recent developments in imaging technology, such as cryo-electron tomography and super-resolution fluorescence microscopy, in gene sequencing technology, and in gene editing technology are rapidly leading to new breakthroughs in our understanding of these questions. A summary is presented of our current understanding of selected aspects of these questions, highlighting areas of uncertainty and contention as well as recent discoveries that provide new insights. Examples of structural data from emerging imaging technologies are presented.

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“…In addition, mutations of RPE65 that prevent formation of visual pigments are expected to lower [Ca 2+ ] due to the constitutive activity of free opsin proteins which continuously stimulate the phototransduction cascade (Woodruff et al, 2003). Other examples of mutations leading to uncontrolled phototransduction and photoreceptor cell death include the rod arrestin knockout (Chen et al, 1999b; Wang and Chen, 2014) and rhodopsin kinase knockout (Chen et al, 1999a) mouse models. Indeed, an “equivalent light” hypothesis has been put forward to explain how the dominantly active mutations in the phototransduction cascade lead to cell death (Fain, 2006; Fain and Lisman, 1993).…”

Section: Role Of Calcium In Photoreceptor Degenerationmentioning

confidence: 99%

Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors

Vinberg

Chen

Kefalov

2018

Progress in Retinal and Eye Research

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Calcium plays important roles in the function and survival of rod and cone photoreceptor cells. Rapid regulation of calcium in the outer segments of photoreceptors is required for the modulation of phototransduction that drives the termination of the flash response as well as light adaptation in rods and cones. On a slower time scale, maintaining proper calcium homeostasis is critical for the health and survival of photoreceptors. Decades of work have established that the level of calcium in the outer segments of rods and cones is regulated by a dynamic equilibrium between influx via the transduction cGMP-gated channels and extrusion via rod- and cone-specific Na+/Ca2+, K+ exchangers (NCKXs). It had been widely accepted that the only mechanism for extrusion of calcium from rod outer segments is via the rod-specific NCKX1, while extrusion from cone outer segments is driven exclusively by the cone-specific NCKX2. However, recent evidence from mice lacking NCKX1 and NCKX2 have challenged that notion and have revealed a more complex picture, including a NCKX-independent mechanism in rods and two separate NCKX-dependent mechanisms in cones. This review will focus on recent findings on the molecular mechanisms of extrusion of calcium from the outer segments of rod and cone photoreceptors, and the functional and structural changes in photoreceptors when normal extrusion is disrupted.

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

Cited by 23 publications

References 54 publications

Guanylate cyclase–activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors

Guanylate cyclase–activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors

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