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.

Problem links

Need precise spatiotemporal control with light input

Derived

Opto-RGS2 is an optogenetic multi-component switch that uses light-induced heterodimerization to recruit the RGS2 domain to the plasma membrane, where it interacts with its cognate G protein. It was developed for studying calcium encoding through optical control of Gq-protein signaling.

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

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: actuatorswitch architecture: multi componentswitch architecture: recruitment

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 8experimental 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 9experimental 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 10experimental 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 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 15functional 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 16functional 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 17functional 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 18functional 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 19functional 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 20functional 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 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 22mechanismsupports2018Source 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 23mechanismsupports2018Source 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 24mechanismsupports2018Source 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 25mechanismsupports2018Source 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 26mechanismsupports2018Source 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 27mechanismsupports2018Source 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 28mechanismsupports2018Source 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 29mechanismsupports2018Source 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 30mechanismsupports2018Source 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 31mechanismsupports2018Source 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 32mechanismsupports2018Source 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 33mechanismsupports2018Source 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 34mechanismsupports2018Source 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 35mechanismsupports2018Source 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 36mechanismsupports2018Source 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 37mechanismsupports2018Source 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 38tool 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 39tool 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 40tool 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 41tool 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 42tool 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 43tool 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 44tool 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 45tool 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 46tool 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 47tool 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.

Compared with LightOn system

light-induced hetero-dimerization system and LightOn system address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: heterodimerization; same primary input modality: light

Compared with photo-activatable Akt probe

light-induced hetero-dimerization system and photo-activatable Akt probe address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: heterodimerization; same primary input modality: light

Compared with tandem-dimer nano (tdnano)

light-induced hetero-dimerization system and tandem-dimer nano (tdnano) address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: heterodimerization; same primary input modality: light

Ranked Citations

  1. 1.
    StructuralSource 1Scholarly Commons (University of Pennsylvania)2018Claim 8Claim 8Claim 8

    Extracted from this source document.