Phototransduction in transgenic mice after targeted deletion of the rod transducin α-subunit

Calvert, Peter D.; Krasnoperova, Nataliia V.; Lyubarsky, Arkady; Isayama, Tomoki; Nicolò, Massimo; Kosaras, Béla; Wong, George S. K.; Gannon, Kimberley S.; Margolskee, Robert F.; Sidman, Richard L.; Pugh, Edward N.; Makino, Clint L.; Lem, Janis

doi:10.1073/pnas.250478897

Cited by 332 publications

(382 citation statements)

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“…In its absence, rod photoreceptors cannot respond to light (Calvert et al, 2000). However, we show that transducin is dispensable for light-triggered arrestin translocation.…”

Section: Discussionmentioning

confidence: 67%

“…On the other hand, photolyzed rhodopsin may signal arrestin movement through molecular motors in a process mediated by transducin signaling and/or transducin translocation. To determine whether these events underlie arrestin movement, we examined arrestin localization in mice defective in rhodopsin phosphorylation (Chen et al, 1999a;Mendez et al, 2000) and subsequently in mice lacking transducin (Calvert et al, 2000). To confirm that lightdependent arrestin movement is signaled through rhodopsin, we examined arrestin localization in retinas from RPE65 Ϫ/Ϫ mice that are deficient in rhodopsin because of a defect in the visual cycle (Redmond et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

“…CSM/rho Ϫ/Ϫ mice (rhodopsin knock-out mice expressing a mutant rhodopsin in which all of the phosphorylation sites at the C terminus were substituted to Ala, or "completely substituted mutant" rhodopsin) were derived at the University of Southern California as described previously (Mendez et al, 2000); RK Ϫ/Ϫ and Arr Ϫ/Ϫ mice were derived at the California Institute of Technology on a C57BL/6 ϫ 129/SvJ background (Xu et al, 1997;Chen et al, 1999a). Tr ␣ Ϫ/Ϫ mice were derived at Tufts University on a BALB/c ϫ 129/SvJ background (Calvert et al, 2000). Mice lacking retinal pigment epithelium 65 (RPE65 Ϫ/Ϫ mice) were kindly provided by Dr. Redmond [National Institutes of Health, Bethesda, MD (Redmond et al, 1998)].…”

Section: Methodsmentioning

confidence: 99%

“…In the absence of transducin, retinal rods maintain their structure, but they do not respond to light (Calvert et al, 2000). Light-dependent arrestin translocation was investigated in mice lacking the transducin ␣ subunit (Tr ␣ Ϫ/Ϫ ) to determine whether transducin signaling is required for arrestin movement (Fig.…”

Section: Transducin Signaling Is Not Required For Light-driven Arrestmentioning

confidence: 99%

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Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

2003

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Visual arrestin plays a crucial role in the termination of the light response in vertebrate photoreceptors by binding selectively to lightactivated, phosphorylated rhodopsin. Arrestin localizes predominantly to the inner segments and perinuclear region of dark-adapted rod photoreceptors, whereas light induces redistribution of arrestin to the rod outer segments. The mechanism by which arrestin redistributes in response to light is not known, but it is thought to be associated with the ability of arrestin to bind photolyzed, phosphorylated rhodopsin in the outer segment. In this study, we show that light-driven translocation of arrestin is unaffected in two different mouse models in which rhodopsin phosphorylation is lacking. We further show that arrestin movement is initiated by rhodopsin but does not require transducin signaling. These results exclude passive diffusion and point toward active transport as the mechanism for lightdependent arrestin movement in rod photoreceptor cells.

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“…In its absence, rod photoreceptors cannot respond to light (Calvert et al, 2000). However, we show that transducin is dispensable for light-triggered arrestin translocation.…”

Section: Discussionmentioning

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Transducin Signaling Is Not Required For Light-driven Arrestmentioning

confidence: 99%

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Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

2003

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“…The mutant animals lacking either rhodopsin kinase or arrestin were mated with another strain of mutant mice that lacked the gene for the rod transducin a subunit. In animals lacking T a , the rods do not respond, (29) since T a is essential for the activation of the PDE (see Fig. 1B).…”

Section: Continuous Light Kills By Activating Transductionmentioning

confidence: 96%

Why photoreceptors die (and why they don't)

Fain

2006

BioEssays

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Light can kill the photoreceptors of the eye, not only very bright direct sunlight, but more moderate illumination if the light is present continuously. Recent experiments show that rod apoptosis can be triggered by strong and constant activation of transduction, and that death can be prevented if transduction is inhibited even though the eye is illuminated. Vitamin A deficiency and genetically inherited diseases, such as some forms of retinitis pigmentosa and Leber congenital amaurosis, appear to kill like this: transduction is activated at a high rate and continuously, and this causes the rods to die. Why does transduction kill? Our best guess is that continuous activation produces a prolonged lowering of the Ca2+ concentration, which is also thought to kill neurons in tissue culture and during the development of the nervous system. To prevent death in constant light, rods have evolved protective mechanisms including modulation of channels and ion transport to keep the Ca2+ from going too low. Prolonged light exposure also causes migration of transduction proteins from one part of the cell to another and a reversible shortening of the rod outer segments, the part of the cell that contains the pigment rhodopsin. All of these mechanisms are at work in the normal eye to reduce transduction and prevent the Ca2+ concentration from dropping too low for too long a time. That most of us retain our vision our entire lives is a testament to their effectiveness. BioEssays 28: 344–354, 2006. © 2006 Wiley Periodicals, Inc.

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B ardet‐ B iedl Syndrome

Slavotinek

2005

Management of Genetic Syndromes

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Bardet‐Biedl syndrome is a rare, pleiotropic congenital malformation syndrome comprising rod‐cone dystrophy, postaxial polydactyly, truncal obesity, learning disability, hypogenitalism, and renal disease. It is an important diagnostic consideration in syndromes with progressive visual impairment or with overgrowth. In the last few years, isolation of seven of the causative genes in this heterogeneous syndrome and the elucidation of possible complex patterns of inheritance have resulted in an increased awareness of Bardet‐Biedl syndrome in the medical and scientific community.

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Phototransduction in transgenic mice after targeted deletion of the rod transducin α-subunit

Abstract: CorrectionsNEUROBIOLOGY. For the article ''Phototransduction in transgenic mice after targeted deletion of the rod transducin ␣-subunit'' by

Cited by 332 publications

References 46 publications

Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

Why photoreceptors die (and why they don't)

B ardet‐ B iedl Syndrome

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