Toolkit/light-induced hetero-dimerization system

light-induced hetero-dimerization system

Multi-Component Switch·Research·Since 2018

Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

Opto-RGS2 is an optogenetic multi-component switch that uses a light-induced heterodimerization system to recruit the RGS2 domain to the plasma membrane, where it interacts with its cognate G protein. It was developed to enable optical control of Gq-protein signaling and associated calcium oscillation dynamics.

Usefulness & Problems

Why this is useful

This system is useful for perturbing Gq-linked signaling with light by controlling membrane recruitment of an RGS2 effector domain. In an engineered cell-line context, it supported optical re-creation of calcium oscillation patterns that independently varied a single waveform component.

Source:

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Source:

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

Problem solved

The tool addresses the problem of controlling G-protein signaling with sufficient temporal precision to study how specific features of calcium oscillations encode information. It specifically enables light-dependent recruitment of RGS2 as a feedback regulator within a Gq-protein signaling circuit.

Source:

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.

Techniques

No technique tags yet.

Target processes

No target processes tagged yet.

Input: Light

Implementation Constraints

Implementation involved engineering a light-induced heterodimerization system that recruits the RGS2 domain to the membrane. The available evidence also indicates use of an optogenetically engineered cell line, a mathematical model, and custom hardware, but does not specify construct architecture, expression system details, or chromophore requirements.

The supplied evidence does not identify the heterodimerization pair, illumination wavelength, kinetic performance, or quantitative dynamic range. Validation is described in an engineered cell line and a calcium-signaling application, with no independent replication or broader organismal testing provided here.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 2experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 3experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 4experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 5experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 6experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 7experimental capabilitysupports2018Source 1needs review

Using a mathematical model, an optogenetically engineered cell line, and custom hardware, the authors optically re-created patterns of calcium oscillations that independently varied a single waveform component.

Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component.
Claim 8functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 9functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 10functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 11functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 12functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 13functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 14functional effectsupports2018Source 1needs review

Using the engineered opto-RGS2 cell line, RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.

Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit.
Claim 15mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 16mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 17mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 18mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 19mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 20mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 21mechanismsupports2018Source 1needs review

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.
Claim 22tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 23tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 24tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 25tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 26tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 27tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.
Claim 28tool developmentsupports2018Source 1needs review

The authors developed optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding.

Approval Evidence

1 source1 linked approval claimfirst-pass slug light-induced-hetero-dimerization-system
A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

Source:

mechanismsupports

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein.

Source:

Comparisons

Source-backed strengths

The reported design provides mechanistic specificity through light-induced membrane recruitment of the RGS2 domain to its site of action at the membrane. In the engineered opto-RGS2 cell line, RGS2 reduced the periodicity and stochasticity of G-protein-coupled calcium oscillations and functioned as a feedback regulator.

Ranked Citations

  1. 1.
    StructuralSource 1Scholarly Commons (University of Pennsylvania)2018Claim 1Claim 2Claim 3

    Extracted from this source document.