Source 1primary paper2023Research Square (Research Square)
Toolkit/PHR domain of Arabidopsis thaliana cryptochrome 2
PHR domain of Arabidopsis thaliana cryptochrome 2
Also known as: Arabidopsis cryptochrome 2, PHR domain
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The PHR domain of Arabidopsis thaliana cryptochrome 2 is a blue-light-responsive protein domain that self-oligomerizes upon illumination. In the cited optogenetic application, it was fused into a construct that rapidly modulated caspase-8 activation, leading to caspase-3 accumulation and induction of apoptosis.
Usefulness & Problems
Why this is useful
This domain is useful as a genetically encoded light input module for rapid optical control of signaling proteins through blue-light-induced self-oligomerization. The cited study used it to achieve precise modulation of caspase-8 activity and to regulate inflammasome activation and pyroptosis under conditions where apoptosis and necroptosis were compromised.
Source:
Our optogenetic tool enables precise modulation of Caspase-8 activity, inducing cellular apoptosis.
Source:
In this study, we developed an optogenetic approach to rapidly modulate the activation of caspase-8 in response to blue light.
Problem solved
It addresses the problem of controlling caspase-8-dependent cell-death signaling with high temporal precision using a noninvasive light stimulus. The supplied evidence specifically supports its use for blue-light-triggered activation of caspase-8 and downstream apoptotic signaling.
Problem links
Need conditional recombination or state switching
DerivedThe PHR domain of Arabidopsis thaliana cryptochrome 2 is a blue-light-responsive protein domain that self-oligomerizes upon illumination. In the cited optogenetic application, this light-induced oligomerization was used to rapidly modulate caspase-8 activity and induce apoptosis.
Need precise spatiotemporal control with light input
DerivedThe PHR domain of Arabidopsis thaliana cryptochrome 2 is a blue-light-responsive protein domain that self-oligomerizes upon illumination. In the cited optogenetic application, this light-induced oligomerization was used to rapidly modulate caspase-8 activity and induce apoptosis.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Mechanisms
light-induced self-oligomerizationlight-induced self-oligomerizationOligomerizationOligomerizationTechniques
No technique tags yet.
Target processes
recombinationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: regulatorswitch architecture: single chain
The evidence supports use of the Arabidopsis thaliana cryptochrome 2 PHR domain as the core light-responsive module in a fusion construct, including a PHR-Caspase8 precursor. Blue light is the activating input, but the supplied evidence does not specify construct architecture beyond fusion, expression system, cofactor requirements, or delivery modality.
The supplied evidence is limited to a specific optogenetic application centered on caspase-8 and cell-death pathways. Practical performance parameters such as activation wavelength range, reversibility, kinetics, dynamic range, background activity, and behavior in other targets or organisms are not provided in the evidence set.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successMammalian Cell Linemechanistic demo
Inferred from claim c2 during normalization. Blue light exposure decreased precursor PHR-Caspase8 abundance and increased activated caspase-8 (P18) and caspase-3 accumulation. Derived from claim c2. Quoted text: After exposure to blue light, the abundance of the precursor protein PHR-Caspase8 decreased, while the activated forms of caspase8 (P18) and caspase3 accumulated.
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c7 during normalization. Under blue light control, the tool regulates inflammasome activation and induces pyroptosis when apoptosis and necroptosis mechanisms are compromised. Derived from claim c7. Quoted text: Additionally, through blue light control, it regulates the activation of the inflammasome and induction of pyroptosis in cases where apoptosis and necroptosis mechanisms are compromised.
Source:
Supporting Sources
Ranked Claims
Under blue light control, the tool regulates inflammasome activation and induces pyroptosis when apoptosis and necroptosis mechanisms are compromised.
Additionally, through blue light control, it regulates the activation of the inflammasome and induction of pyroptosis in cases where apoptosis and necroptosis mechanisms are compromised.
Blue light exposure decreased precursor PHR-Caspase8 abundance and increased activated caspase-8 (P18) and caspase-3 accumulation.
After exposure to blue light, the abundance of the precursor protein PHR-Caspase8 decreased, while the activated forms of caspase8 (P18) and caspase3 accumulated.
The optogenetic tool enables precise modulation of caspase-8 activity to induce cellular apoptosis.
Our optogenetic tool enables precise modulation of Caspase-8 activity, inducing cellular apoptosis.
The study developed an optogenetic approach that rapidly modulates caspase-8 activation in response to blue light.
In this study, we developed an optogenetic approach to rapidly modulate the activation of caspase-8 in response to blue light.
Approval Evidence
1 source4 linked approval claimsfirst-pass slug phr-domain-of-arabidopsis-thaliana-cryptochrome-2
The core component of our optogenetic tool is based on the PHR domain of Arabidopsis thaliana cryptochrome 2, which self-oligomerizes in response to blue light.
Source:
conditional functionsupports
Under blue light control, the tool regulates inflammasome activation and induces pyroptosis when apoptosis and necroptosis mechanisms are compromised.
Additionally, through blue light control, it regulates the activation of the inflammasome and induction of pyroptosis in cases where apoptosis and necroptosis mechanisms are compromised.
Source:
mechanistic effectsupports
Blue light exposure decreased precursor PHR-Caspase8 abundance and increased activated caspase-8 (P18) and caspase-3 accumulation.
After exposure to blue light, the abundance of the precursor protein PHR-Caspase8 decreased, while the activated forms of caspase8 (P18) and caspase3 accumulated.
Source:
tool functionsupports
The optogenetic tool enables precise modulation of caspase-8 activity to induce cellular apoptosis.
Our optogenetic tool enables precise modulation of Caspase-8 activity, inducing cellular apoptosis.
Source:
tool functionsupports
The study developed an optogenetic approach that rapidly modulates caspase-8 activation in response to blue light.
In this study, we developed an optogenetic approach to rapidly modulate the activation of caspase-8 in response to blue light.
Source:
Comparisons
Source-backed strengths
The reported tool responds to blue light and rapidly modulates caspase-8 activation. Experimental evidence cited for the application showed decreased precursor PHR-Caspase8 abundance together with increased activated caspase-8 (P18) and caspase-3 accumulation, consistent with functional induction of apoptosis.
Compared with AQTrip EL222 variant
PHR domain of Arabidopsis thaliana cryptochrome 2 and AQTrip EL222 variant address a similar problem space because they share recombination.
Shared frame: shared target processes: recombination; shared mechanisms: oligomerization; same primary input modality: light
Strengths here: looks easier to implement in practice.
Compared with DspA
PHR domain of Arabidopsis thaliana cryptochrome 2 and DspA address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; same primary input modality: light
Compared with melanopsin
PHR domain of Arabidopsis thaliana cryptochrome 2 and melanopsin address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.
Derived from 4 linked claims and 2 validation observations. Example evidence: Additionally, through blue light control, it regulates the activation of the inflammasome and induction of pyroptosis in cases where apoptosis and necroptosis mechanisms are compromised.