Source 1primary paper2019
Toolkit/tandem-dimer nano (tdnano)
tandem-dimer nano (tdnano)
Also known as: tdnano
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
tdnano is a constructed tandem-dimer of the iLID binding partner nano used as the second component of a blue-light-responsive iLID system. In the reported opto-receptor tyrosine kinase designs, blue light drives recruitment of two iLID-fused RTK molecules to tdnano, enabling receptor dimerization and activation.
Usefulness & Problems
Why this is useful
tdnano provides a modular way to convert the iLID light-induced interaction into enforced pairing of two receptor tyrosine kinase molecules. In the reported opto-iTrkA and opto-iTrkB systems, this enabled light-dependent activation of downstream ERK and Akt signaling and supported multi-day, population-level TrkA activation in PC12 cells.
Problem solved
A central challenge for optogenetic control of RTKs is achieving light-dependent receptor dimerization in a defined multi-component format. tdnano addresses this by presenting a tandem nano scaffold that recruits two copies of iLID-RTK under blue light, thereby coupling iLID binding to RTK activation.
Problem links
Need conditional control of signaling activity
Derivedtdnano is a constructed tandem-dimer of the iLID binding partner nano used as the second component of a blue-light-responsive iLID system. In the reported opto-RTK designs, tdnano recruits two copies of iLID-fused receptor tyrosine kinase constructs under blue light, enabling receptor dimerization and activation.
Need precise spatiotemporal control with light input
Derivedtdnano is a constructed tandem-dimer of the iLID binding partner nano used as the second component of a blue-light-responsive iLID system. In the reported opto-RTK designs, tdnano recruits two copies of iLID-fused receptor tyrosine kinase constructs under blue light, enabling receptor dimerization and activation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
HeterodimerizationHeterodimerizationHeterodimerizationinduced dimerizationinduced dimerizationlight-induced recruitmentlight-induced recruitmentTechniques
No technique tags yet.
Target processes
signalingInput: 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: regulatorswitch architecture: multi componentswitch architecture: recruitment
tdnano is implemented as a constructed tandem-dimer of nano and functions as the binding partner component for iLID-based blue-light control. The reported use case requires co-expression with iLID-fused RTK constructs, where blue light induces recruitment of two iLID-RTK molecules to tdnano.
The available evidence is limited to a single 2019 study and specifically to opto-iTrkA and opto-iTrkB implementations. Quantitative performance characteristics, broader receptor compatibility, and independent replication are not provided in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 source3 linked approval claimsfirst-pass slug tandem-dimer-nano-tdnano
with a constructed tandem-dimer of its binding partner nano (tdnano)
Source:
activitysupports
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.
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:
targetingsupports
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
Source:
Comparisons
Source-backed strengths
The reported system reproduced downstream ERK and Akt signaling for opto-iTrkA and opto-iTrkB only in the presence of tdnano, supporting its functional necessity in these designs. It was also reported to be compatible with multi-day and population-level activation of TrkA in PC12 cells.
Compared with fusion proteins with large N-terminal anchors
tandem-dimer nano (tdnano) and fusion proteins with large N-terminal anchors address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: heterodimerization; same primary input modality: light
Compared with iLID/SspB
tandem-dimer nano (tdnano) and iLID/SspB address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: heterodimerization; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with LOVpep/ePDZb
tandem-dimer nano (tdnano) and LOVpep/ePDZb address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: heterodimerization; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.