scholarly journals Elementary response triggered by transducin in retinal rods

2019 ◽  
Vol 116 (11) ◽  
pp. 5144-5153 ◽  
Author(s):  
Wendy W. S. Yue ◽  
Daniel Silverman ◽  
Xiaozhi Ren ◽  
Rikard Frederiksen ◽  
Kazumi Sakai ◽  
...  
Keyword(s):  
G Protein ◽  
Single Photon ◽  
High Gain ◽  
Intact Mouse ◽  
Physiological Processes ◽  
Retinal Rods ◽  
Retinal Rod ◽  
Elementary Response ◽  
Electrical Effect ◽  
Single Photon Response

G protein-coupled receptor (GPCR) signaling is crucial for many physiological processes. A signature of such pathways is high amplification, a concept originating from retinal rod phototransduction, whereby one photoactivated rhodopsin molecule (Rho*) was long reported to activate several hundred transducins (GT*s), each then activating a cGMP-phosphodiesterase catalytic subunit (GT*·PDE*). This high gain at the Rho*-to-GT* step has been challenged more recently, but estimates remain dispersed and rely on some nonintact rod measurements. With two independent approaches, one with an extremely inefficient mutant rhodopsin and the other with WT bleached rhodopsin, which has exceedingly weak constitutive activity in darkness, we obtained an estimate for the electrical effect from a single GT*·PDE* molecular complex in intact mouse rods. Comparing the single-GT*·PDE* effect to the WT single-photon response, both in Gcaps−/− background, gives an effective gain of only ∼12–14 GT*·PDE*s produced per Rho*. Our findings have finally dispelled the entrenched concept of very high gain at the receptor-to-G protein/effector step in GPCR systems.

scholarly journals Local, nonlinear effects of cGMP and Ca2+ reduce single photon response variability in retinal rods

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0225948 ◽  
Author(s):  
Giovanni Caruso ◽  
Vsevolod V. Gurevich ◽  
Colin Klaus ◽  
Heidi Hamm ◽  
Clint L. Makino ◽  
...  
Keyword(s):  
Single Photon ◽  
Nonlinear Effects ◽  
Response Variability ◽  
Retinal Rods ◽  
Single Photon Response

scholarly journals Determinants of single photon response variability.

1994 ◽  
Vol 103 (4) ◽  
pp. 679-690 ◽  
Author(s):  
A Kirkwood ◽  
J E Lisman
Keyword(s):  
Size Distribution ◽  
Exponential Distribution ◽  
G Protein ◽  
G Proteins ◽  
Single Photon ◽  
Companion Paper ◽  
Single Step ◽  
Size Distributions ◽  
Step Process ◽  
Single Photon Response

The responses to single photon absorptions (quantum bumps) vary randomly in size in Limulus photoreceptors. This variability is a natural consequence of simple chemical reactions involving a small number of molecules. The measured size distributions differ significantly from the exponential distribution predicted by the simplest transduction cascade models, one feature of which is that light-activated rhodopsin (R*) is turned off in a single step process. As shown in the companion paper, the nonexponential size distributions can be accounted for if R* is turned off in a multi-step process. This would lead to a nonexponential (peaked) distribution in the number of G-protein molecules activated during a quantum bump and to a nonexponential distribution in the size of bumps. To test this possibility we measured the distribution of quantum bump size under two conditions in which the variability in the number of activated G-proteins was eliminated. eliminated. In one method, bumps were produced by direct activation of single G-proteins using GTP-gamma-S; in the second GDP-beta-S reduced the R* gain to the point where most quantal events were due to activation of a single G-protein. In both cases the size distribution of bumps became much closer to an exponential distribution than that of normal light-induced bumps. These results support the idea that the size distribution of light-induced bumps is dependent on events at the R* level and reflects to the multi-step deactivation of R*.

scholarly journals Nano-optical single-photon response mapping of waveguide integrated molybdenum silicide (MoSi) superconducting nanowires

2016 ◽  
Vol 24 (13) ◽  
pp. 13931 ◽  
Author(s):  
Jian Li ◽  
Robert A. Kirkwood ◽  
Luke J. Baker ◽  
David Bosworth ◽  
Kleanthis Erotokritou ◽  
...  
Keyword(s):  
Single Photon ◽  
Molybdenum Silicide ◽  
Superconducting Nanowires ◽  
Response Mapping ◽  
Single Photon Response

Research progress of infrared single-photon detection with high gain (Invited)

2021 ◽  
Vol 50 (1) ◽  
pp. 20211016-20211016
Author(s):  
吴静远 Jingyuan Wu ◽  
刘肇国 Zhaoguo Liu ◽  
张彤 Tong Zhang
Keyword(s):  
Single Photon ◽  
High Gain ◽  
Research Progress ◽  
Single Photon Detection ◽  
Photon Detection

scholarly journals Simultaneous high-speed imaging and optogenetic inhibition in the intact mouse brain

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Serena Bovetti ◽  
Claudio Moretti ◽  
Stefano Zucca ◽  
Marco Dal Maschio ◽  
Paolo Bonifazi ◽  
...  
Keyword(s):  
Mouse Brain ◽  
High Speed ◽  
Pyramidal Neurons ◽  
Functional Organization ◽  
Single Photon ◽  
Electrophysiological Recording ◽  
Mammalian Brain ◽  
Cellular Mechanisms ◽  
High Speed Imaging ◽  
Intact Mouse

Abstract Genetically encoded calcium indicators and optogenetic actuators can report and manipulate the activity of specific neuronal populations. However, applying imaging and optogenetics simultaneously has been difficult to establish in the mammalian brain, even though combining the techniques would provide a powerful approach to reveal the functional organization of neural circuits. Here, we developed a technique based on patterned two-photon illumination to allow fast scanless imaging of GCaMP6 signals in the intact mouse brain at the same time as single-photon optogenetic inhibition with Archaerhodopsin. Using combined imaging and electrophysiological recording, we demonstrate that single and short bursts of action potentials in pyramidal neurons can be detected in the scanless modality at acquisition frequencies up to 1 kHz. Moreover, we demonstrate that our system strongly reduces the artifacts in the fluorescence detection that are induced by single-photon optogenetic illumination. Finally, we validated our technique investigating the role of parvalbumin-positive (PV) interneurons in the control of spontaneous cortical dynamics. Monitoring the activity of cellular populations on a precise spatiotemporal scale while manipulating neuronal activity with optogenetics provides a powerful tool to causally elucidate the cellular mechanisms underlying circuit function in the intact mammalian brain.

scholarly journals Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases

2018 ◽  
Vol 115 (30) ◽  
pp. E7033-E7042 ◽  
Author(s):  
Mattia Malvezzi ◽  
Kiran K. Andra ◽  
Kalpana Pandey ◽  
Byoung-Cheol Lee ◽  
Maria E. Falzone ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
G Protein ◽  
Credit Card ◽  
Protein Families ◽  
G Protein Coupled Receptor ◽  
Physiological Processes ◽  
Phospholipid Scrambling ◽  
Conformational Rearrangements ◽  
G Protein Coupled ◽  
Gpcr Protein

Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card” mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.

Research progress of infrared single-photon detection with high gain (Invited)

2021 ◽  
Vol 50 (1) ◽  
pp. 20211016-20211016
Author(s):  
吴静远 Jingyuan Wu ◽  
刘肇国 Zhaoguo Liu ◽  
张彤 Tong Zhang
Keyword(s):  
Single Photon ◽  
High Gain ◽  
Research Progress ◽  
Single Photon Detection ◽  
Photon Detection

Identification Methods of G Protein-Coupled Receptors

2011 ◽  
Vol 2 (4) ◽  
pp. 35-52
Author(s):  
Meriem Zekri ◽  
Karima Alem ◽  
Labiba Souici-Meslati
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Pharmaceutical Research ◽  
G Protein Coupled Receptors ◽  
Machine Learning Algorithms ◽  
Signaling Networks ◽  
Identification Methods ◽  
Physiological Processes ◽  
Cell Signaling Networks ◽  
G Protein Coupled

The G protein-coupled receptors (GPCRs) include one of the largest and most important families of multifunctional proteins known to molecular biology. They play a key role in cell signaling networks that regulate many physiological processes, such as vision, smell, taste, neurotransmission, secretion, immune responses, metabolism, and cell growth. These proteins are thus very important for understanding human physiology and they are involved in several diseases. Therefore, many efforts in pharmaceutical research are to understand their structures and functions, which is not an easy task, because although thousands GPCR sequences are known, many of them remain orphans. To remedy this, many methods have been developed using methods such as statistics, machine learning algorithms, and bio-inspired approaches. In this article, the authors review the approaches used to develop algorithms for classification GPCRs by trying to highlight the strengths and weaknesses of these different approaches and providing a comparison of their performances.

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