Source 1primary paper2023Molecular Brain
Toolkit/optoRET
optoRET
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
optoRET is an optogenetic RET signaling switch created by fusing the cytosolic region of human RET to a blue-light-inducible homo-oligomerizing protein. Blue-light stimulation modulates RET pathway output, including Grb2 recruitment and activation of AKT and ERK, and can also induce local filopodia-like F-actin structures through Cdc42 activation.
Usefulness & Problems
Why this is useful
optoRET enables light-dependent control of RET signaling with temporal precision, as varying photoactivation duration was reported to dynamically modulate pathway output. It was also used to modulate RET signaling in dopaminergic neurons of the mouse substantia nigra, indicating utility for probing signaling function in neuronal contexts and in vivo.
Source:
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
Source:
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
Source:
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
Problem solved
optoRET addresses the problem of controlling RET signaling with spatiotemporal precision rather than relying on static or diffusible inputs. The reported local induction of filopodia-like F-actin structures at stimulated regions indicates that it can be used to dissect localized RET-dependent morphological responses.
Source:
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
Source:
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
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
signalingInput: Light
Implementation Constraints
The reported design combines the cytosolic region of human RET with a blue-light-inducible homo-oligomerizing protein, so implementation requires expression of this fusion construct and blue-light illumination. The available evidence supports use in cultured neurons and in dopaminergic neurons of the mouse substantia nigra, but does not provide further details on delivery method, promoter choice, or cofactor requirements.
The supplied evidence is limited to a single 2023 study and a brief construct description, so quantitative performance metrics, reversibility, background activity, and spectral constraints are not established here. The identity of the blue-light-inducible homo-oligomerizing module and detailed construct architecture are also not provided in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
Approval Evidence
1 source7 linked approval claimsfirst-pass slug optoret
we developed an optogenetic tool for modulating RET signaling, termed optoRET, combining the cytosolic region of human RET with a blue-light-inducible homo-oligomerizing protein
Source:
dynamic controlsupports
Varying the duration of photoactivation enabled dynamic modulation of RET signaling by optoRET.
By varying the duration of photoactivation, we were able to dynamically modulate RET signaling.
Source:
in vivo modulationsupports
The study successfully modulated RET signaling with optoRET in dopaminergic neurons of the substantia nigra in the mouse brain.
Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain.
Source:
morphological effectsupports
Local optoRET activation triggered formation of filopodia-like F-actin structures at stimulated regions through Cdc42 activation.
trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation
Source:
signaling activationsupports
Activation of optoRET recruited Grb2 and stimulated AKT and ERK in cultured neurons, with robust and efficient ERK activation.
Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation.
Source:
subcellular signal propagationsupports
Local activation of the distal part of the neuron retrogradely transduced AKT and ERK signals to the soma.
By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma
Source:
therapeutic potentialsupports
optoRET has potential to be developed as a therapeutic intervention for modulating RET downstream signaling with light.
Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
Source:
tool developmentsupports
The study developed optoRET, an optogenetic tool for modulating RET signaling.
In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET
Source:
Comparisons
Source-backed strengths
The tool was reported to support dynamic modulation of RET signaling by changing the duration of blue-light photoactivation. It also showed application in dopaminergic neurons in the mouse brain and produced localized morphological effects, including filopodia-like protrusions associated with Cdc42 activation.
Ranked Citations
- 1.