scholarly journals Phosducin Regulates the Expression of Transducin βγ Subunits in Rod Photoreceptors and Does Not Contribute to Phototransduction Adaptation

2007 ◽  
Vol 130 (3) ◽  
pp. 303-312 ◽  
Author(s):  
Claudia M. Krispel ◽  
Maxim Sokolov ◽  
Yen-Ming Chen ◽  
Hongman Song ◽  
Rolf Herrmann ◽  
...  
Keyword(s):  
G Protein ◽  
Outer Segment ◽  
Light Adaptation ◽  
Wild Type ◽  
Rod Photoreceptors ◽  
Response Properties ◽  
Adaptation Mechanisms ◽  
Subunit Expression

For over a decade, phosducin's interaction with the βγ subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcited rhodopsin. In this study we directly tested this hypothesis by characterizing the dark- and light-adapted response properties of phosducin knockout (Pd−/−) rods. Pd−/− rods were notably less sensitive to light than wild-type (WT) rods. The gain of transduction, as measured by the amplification constant using the Lamb-Pugh model of activation, was 32% lower in Pd−/− rods than in WT rods. This reduced amplification correlated with a 36% reduction in the level of transducin βγ-subunit expression, and thus available heterotrimer in Pd−/− rods. However, commonly studied forms of light adaptation were normal in the absence of phosducin. Thus, phosducin does not appear to contribute to adaptation mechanisms of the outer segment by dynamically controlling heterotrimer availability, but rather is necessary for maintaining normal transducin expression and therefore normal flash sensitivity in rods.

scholarly journals Protein Kinase C Activity and Light Sensitivity of Single Amphibian Rods

1997 ◽  
Vol 110 (4) ◽  
pp. 441-452 ◽  
Author(s):  
W.-H. Xiong ◽  
K. Nakatani ◽  
B. Ye ◽  
K.-W. Yau
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Outer Segment ◽  
Light Adaptation ◽  
Light Sensitivity ◽  
Rod Photoreceptors ◽  
Physiological Conditions ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Phototransduction Cascade

Biochemical experiments by others have indicated that protein kinase C activity is present in the rod outer segment, with potential or demonstrated targets including rhodopsin, transducin, cGMP-phosphodiesterase (PDE), guanylate cyclase, and arrestin, all of which are components of the phototransduction cascade. In particular, PKC phosphorylations of rhodopsin and the inhibitory subunit of PDE (PDE γ) have been studied in some detail, and suggested to have roles in downregulating the sensitivity of rod photoreceptors to light during illumination. We have examined this question under physiological conditions by recording from a single, dissociated salamander rod with a suction pipette while exposing its outer segment to the PKC activators phorbol-12-myristate,13-acetate (PMA) or phorbol-12,13-dibutyrate (PDBu), or to the PKC-inhibitor GF109203X. No significant effect of any of these agents on rod sensitivity was detected, whether in the absence or presence of a background light, or after a low bleach. These results suggest that PKC probably does not produce any acute downregulation of rod sensitivity as a mechanism of light adaptation, at least for isolated amphibian rods.

Adaptation in Vertebrate Photoreceptors

2001 ◽  
Vol 81 (1) ◽  
pp. 117-151 ◽  
Author(s):  
Gordon L. Fain ◽  
Hugh R. Matthews ◽  
M. Carter Cornwall ◽  
Yiannis Koutalos
Keyword(s):  
G Protein ◽  
Outer Segment ◽  
Light Adaptation ◽  
Electrical Response ◽  
Light Level ◽  
Free Concentration ◽  
Background Adaptation ◽  
Vertebrate Photoreceptor ◽  
Intracellular Ca ◽  
The One

When light is absorbed within the outer segment of a vertebrate photoreceptor, the conformation of the photopigment rhodopsin is altered to produce an activated photoproduct called metarhodopsin II or Rh*. Rh* initiates a transduction cascade similar to that for metabotropic synaptic receptors and many hormones; the Rh*activates a heterotrimeric G protein, which in turn stimulates an effector enzyme, a cyclic nucleotide phosphodiesterase. The phosphodiesterase then hydrolyzes cGMP, and the decrease in the concentration of free cGMP reduces the probability of opening of channels in the outer segment plasma membrane, producing the electrical response of the cell. Photoreceptor transduction can be modulated by changes in the mean light level. This process, called light adaptation (or background adaptation), maintains the working range of the transduction cascade within a physiologically useful region of light intensities. There is increasing evidence that the second messenger responsible for the modulation of the transduction cascade during background adaptation is primarily, if not exclusively, Ca2+, whose intracellular free concentration is decreased by illumination. The change in free Ca2+ is believed to have a variety of effects on the transduction mechanism, including modulation of the rate of the guanylyl cyclase and rhodopsin kinase, alteration of the gain of the transduction cascade, and regulation of the affinity of the outer segment channels for cGMP. The sensitivity of the photoreceptor is also reduced by previous exposure to light bright enough to bleach a substantial fraction of the photopigment in the outer segment. This form of desensitization, called bleaching adaptation (the recovery from which is known as dark adaptation), seems largely to be due to an activation of the transduction cascade by some form of bleached pigment. The bleached pigment appears to activate the G protein transducin directly, although with a gain less than Rh*. The resulting decrease in intracellular Ca2+ then modulates the transduction cascade, by a mechanism very similar to the one responsible for altering sensitivity during background adaptation.

Movement of retinal along cone and rod photoreceptors

1994 ◽  
Vol 11 (2) ◽  
pp. 389-399 ◽  
Author(s):  
Jing Jin ◽  
Gregor J. Jones ◽  
M. Carter Cornwall
Keyword(s):  
Cell Body ◽  
Dark Adaptation ◽  
Visual Pigment ◽  
Outer Segment ◽  
Light Adaptation ◽  
Rod Photoreceptors ◽  
Rod Outer Segment ◽  
Rods And Cones ◽  
Outer Segments ◽  
Rod Cell

AbstractSingle isolated photoreceptors can be taken through a visual cycle of light adaptation by bleaching visual pigment, followed by dark adaptation when supplied with 11–cis retinal. Light adaptation after bleaching is manifested by faster response kinetics and a permanent reduction in sensitivity to light flashes, presumed to be due to the presence of bleached visual pigment. The recovery of flash sensitivity during dark adaptation is assumed to be due to regeneration of visual pigment to pre-bleach levels. In previous work, the outer segments of bleached, light-adapted cells were exposed to 11–cis retinal. In the present work, the cell bodies of bleached photoreceptors were exposed. We report a marked difference between rods and cones. Bleached cones recover sensitivity when their cell bodies are exposed to 11–cis retinal. Bleached rods do not. These results imply that retinal can move freely along the cone photoreceptor, but retinal either is not taken up by the rod cell body or retinal cannot move from the rod cell body to the rod outer segment. The free transfer of retinal along cone but not along rod photoreceptors could explain why, during dark adaptation in the retina, cones have access to a store of 11–cis retinal which is not available to rods. Additional experiments investigated the movement of retinal along bleached rod outer segments. The results indicate that retinal can move along the rod outer segment, but that this movement is slow, occurring at about the same rate as the regeneration of visual pigment.

scholarly journals Rhodopsin kinase and recoverin modulate phosphodiesterase during mouse photoreceptor light adaptation

2015 ◽  
Vol 145 (3) ◽  
pp. 213-224 ◽  
Author(s):  
Ching-Kang Chen ◽  
Michael L. Woodruff ◽  
Gordon L. Fain
Keyword(s):  
G Protein ◽  
Outer Segment ◽  
Light Adaptation ◽  
Prolonged Exposure ◽  
Genetic Manipulation ◽  
Electrical Response ◽  
Light Response ◽  
Background Light ◽  
Rhodopsin Kinase ◽  
Pde Inhibition

Light stimulates rhodopsin in a retinal rod to activate the G protein transducin, which binds to phosphodiesterase (PDE), relieving PDE inhibition and decreasing guanosine 3′,5′-cyclic monophosphate (cGMP) concentration. The decrease in cGMP closes outer segment channels, producing the rod electrical response. Prolonged exposure to light decreases sensitivity and accelerates response kinetics in a process known as light adaptation, mediated at least in part by a decrease in outer segment Ca2+. Recent evidence indicates that one of the mechanisms of adaptation in mammalian rods is down-regulation of PDE. To investigate the effect of light and a possible role of rhodopsin kinase (G protein–coupled receptor kinase 1 [GRK1]) and the GRK1-regulating protein recoverin on PDE modulation, we used transgenic mice with decreased expression of GTPase-accelerating proteins (GAPs) and, consequently, a less rapid decay of the light response. This slowed decay made the effects of genetic manipulation of GRK1 and recoverin easier to observe and interpret. We monitored the decay of the light response and of light-activated PDE by measuring the exponential response decay time (τREC) and the limiting time constant (τD), the latter of which directly reflects light-activated PDE decay under the conditions of our experiments. We found that, in GAP-underexpressing rods, steady background light decreased both τREC and τD, and the decrease in τD was nearly linear with the decrease in amplitude of the outer segment current. Background light had little effect on τREC or τD if the gene for recoverin was deleted. Moreover, in GAP-underexpressing rods, increased GRK1 expression or deletion of recoverin produced large and highly significant accelerations of τREC and τD. The simplest explanation of our results is that Ca2+-dependent regulation of GRK1 by recoverin modulates the decay of light-activated PDE, and that this modulation is responsible for acceleration of response decay and the increase in temporal resolution of rods in background light.

scholarly journals Increased Notch 1 Expression and Attenuated Stimulatory G Protein Coupling to Adenylyl Cyclase in Osteonectin-Null Osteoblasts

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1666-1674 ◽  
Author(s):  
Catherine B. Kessler ◽  
Anne M. Delany
Keyword(s):  
Adenylyl Cyclase ◽  
G Protein ◽  
Cell Fate ◽  
Osteoblastic Cells ◽  
Matricellular Protein ◽  
Wild Type ◽  
Notch 1 ◽  
Matrix Assembly ◽  
G Protein Coupling ◽  
Protein Coupling

Osteonectin, or secreted protein acidic and rich in cysteine, is one of the most abundant noncollagen matrix components in bone. This matricellular protein regulates extracellular matrix assembly and maturation in addition to modulating cell behavior. Mice lacking osteonectin develop severe low-turnover osteopenia, and in vitro studies of osteonectin-null osteoblastic cells showed that osteonectin supports osteoblast formation, maturation, and survival. The present studies demonstrate that osteonectin-null osteoblastic cells have increased expression of Notch 1, a well-documented regulator of cell fate in multiple systems. Furthermore, osteonectin-null cells are more plastic and less committed to osteoblastic differentiation, able to pursue adipogenic differentiation given the appropriate signals. Notch 1 transcripts are down-regulated by inducers of cAMP in both wild-type and osteonectin-null osteoblasts, suggesting that the mutant osteoblasts may have a defect in generation of cAMP in response to stimuli. Indeed, many bone anabolic agents signal through increased cAMP. Wild-type and osteonectin-null osteoblasts generated comparable amounts of cAMP in response to forskolin, a direct stimulator of adenylyl cyclase. However, the ability of osteonectin-null osteoblasts to generate cAMP in response to cholera toxin, a direct stimulator of Gs, was attenuated. These data imply that osteonectin-null osteoblasts have decreased coupling of Gs to adenylyl cyclase. Because osteonectin promotes G protein coupling to an effector, our studies support the concept that low-turnover osteopenia can result from reducing G protein coupled receptor activity.

Sign in / Sign up

Export Citation Format

Share Document