Toolkit/iLID-RTK

iLID-RTK

Multi-Component Switch·Research·Since 2019

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

Summary

iLID-RTK is a blue-light-controlled, multi-component receptor tyrosine kinase switch built from the iLID and tdnano system. In darkness it is cytosolic, monomeric, and inactive, while blue light recruits two iLID-RTK molecules to tdnano to drive RTK dimerization and activation.

Usefulness & Problems

Why this is useful

This system enables optical control of receptor tyrosine kinase signaling by coupling blue light to inducible receptor dimerization. Reported opto-iTrkA and opto-iTrkB constructs reproduce downstream ERK and Akt signaling only when tdnano is present, indicating utility for conditional pathway activation with spatial and temporal light input.

Problem solved

It addresses the problem of activating RTKs on demand without constitutive receptor clustering in the dark state. The design specifically solves how to keep the receptor module cytosolic, monomeric, and inactive until blue-light-triggered recruitment to a dimerizing scaffold occurs.

Problem links

Need precise spatiotemporal control with light input

Derived

iLID-RTK is a blue-light-controlled, multi-component receptor tyrosine kinase switch built on the iLID plus tdnano system. In the dark it is cytosolic, monomeric, and inactive, whereas blue light recruits two iLID-RTK molecules to tdnano to drive RTK dimerization and activation.

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

The switch is multi-component and requires both an iLID-RTK construct and the tdnano partner for activity. Blue light is the input modality, and activation depends on light-driven recruitment of two iLID-RTK copies to tdnano; PC12-cell compatibility was reported for opto-iTrkA during multi-day and population-level activation.

The evidence provided comes from a single 2019 source and focuses on neurotrophin receptor implementations, specifically opto-iTrkA and opto-iTrkB. Quantitative performance metrics, reversibility kinetics, spectral constraints beyond blue light, and validation across diverse cell types or in vivo settings are not provided in the supplied evidence.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 2activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 3activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 4activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 5activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 6activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 7activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 8activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 9activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 10activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 11compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 12compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 13compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 14compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 15compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 16compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 17compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 18compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 19compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 20compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 21mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 22mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 23mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 24mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 25mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 26mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 27mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 28mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 29mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 30mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 31mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 32mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 33mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 34mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 35mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 36mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 37mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 38mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 39mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 40mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 41mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 42mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 43mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 44mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 45mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 46mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 47mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 48mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 49mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 50mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 51mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 52mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 53mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 54mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 55targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 56targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 57targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 58targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 59targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 60targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 61targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 62targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 63targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 64targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination

Approval Evidence

1 source2 linked approval claimsfirst-pass slug ilid-rtk
In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.

Source:

mechanismsupports

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.

Source:

mechanismsupports

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Source:

Comparisons

Source-backed strengths

The reported dark state is explicitly cytosolic, monomeric, and inactive, supporting low basal activity. In the cited study, opto-iTrkA was compatible with multi-day and population-level activation in PC12 cells, and opto-iTrkA/opto-iTrkB reproduced ERK and Akt signaling only in the presence of tdnano.

Compared with LightOn system

iLID-RTK 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 mOptoT7

iLID-RTK and mOptoT7 address a similar problem space.

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

Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.

iLID-RTK 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.

    Extracted from this source document.