Source 1primary paper2020
Toolkit/light-controlled optogenetic CD3ζ clustering tool
light-controlled optogenetic CD3ζ clustering tool
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The light-controlled optogenetic CD3ζ clustering tool is a multi-component optogenetic system engineered to induce spatial clustering of CD3ζ chains with light. In the cited 2020 study, light-driven CD3ζ clustering was sufficient to initiate proximal T cell receptor signaling, including CD3ζ phosphorylation and recruitment of the tandem SH2 domain of Zap70 to plasma membrane clusters.
Usefulness & Problems
Why this is useful
This tool is useful for testing whether spatial organization of CD3ζ is sufficient to trigger early T cell receptor signaling independently of full receptor engagement. It provides a light-gated way to control signaling localization and onset in reconstituted or cellular systems.
Problem solved
It addresses the mechanistic problem of whether clustering of CD3ζ can itself initialize proximal T cell receptor signaling. The cited work specifically used the system to isolate clustering as a candidate biophysical trigger for CD3ζ phosphorylation and Zap70 recruitment.
Problem links
Need conditional control of signaling activity
DerivedThe light-controlled optogenetic CD3ζ clustering tool is a multi-component optogenetic system engineered to induce spatial clustering of CD3ζ chains with light. In the cited study, CD3ζ clustering was sufficient to initiate proximal T cell receptor signaling, including recruitment of Zap70 tandem SH2 domains and activation of downstream phosphorylation and Ca2+ flux.
Need inducible protein relocalization or recruitment
DerivedThe light-controlled optogenetic CD3ζ clustering tool is a multi-component optogenetic system engineered to induce spatial clustering of CD3ζ chains with light. In the cited study, CD3ζ clustering was sufficient to initiate proximal T cell receptor signaling, including recruitment of Zap70 tandem SH2 domains and activation of downstream phosphorylation and Ca2+ flux.
Need precise spatiotemporal control with light input
DerivedThe light-controlled optogenetic CD3ζ clustering tool is a multi-component optogenetic system engineered to induce spatial clustering of CD3ζ chains with light. In the cited study, CD3ζ clustering was sufficient to initiate proximal T cell receptor signaling, including recruitment of Zap70 tandem SH2 domains and activation of downstream phosphorylation and Ca2+ flux.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
cd3ζ phosphorylation-dependent signal initiationlight-induced spatial clusteringlight-induced spatial clusteringprotein clusteringprotein clusteringrecruitment of zap70 tandem sh2 domains to clustered cd3ζrecruitment of zap70 tandem sh2 domains to clustered cd3ζsignal initiation through cd3ζ phosphorylationTechniques
No technique tags yet.
Target processes
localizationsignalingInput: 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
The tool is described as a multi-component optogenetic construct that clusters CD3ζ chains in response to light. The available evidence indicates use in reconstituted COS-7 cells and dependence on Lck expression for phosphorylation initiation in that context, but specific light wavelength, fusion domains, and delivery or expression details are not provided.
The supplied evidence is limited to a single cited study and a small set of mechanistic claims. Details on photophysical parameters, construct architecture, dynamic range, reversibility, and validation across multiple cell types or in vivo settings are not provided here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Approval Evidence
1 source5 linked approval claimsfirst-pass slug light-controlled-optogenetic-cd3-clustering-tool
Here, we constructed an optogenetic tool that induces spatial clustering of CD3ζ chains in a light controlled manner.
Source:
mechanistic interpretationsupports
Clustering of the TCR can initialize proximal TCR signaling and may constitute a biophysical mechanism of TCR triggering.
Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Source:
minimal requirementsupports
In reconstituted COS-7 cells, Lck expression alone was required to initiate CD3ζ phosphorylation upon CD3ζ clustering.
In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering
Source:
recruitmentsupports
CD3ζ clustering leads to recruitment of the tandem SH2 domain of Zap70 from the cytosol to CD3ζ clusters at the plasma membrane.
which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane
Source:
signaling activationsupports
Spatial clustering of CD3ζ induces phosphorylation of CD3ζ, Zap70, PLCγ, and ERK and initiates Ca2+ flux.
including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux
Source:
sufficiencysupports
Spatial clustering of the CD3ζ intracellular tail alone is sufficient to initiate T cell triggering.
We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering
Source:
Comparisons
Source-backed strengths
The reported system directly induced spatial clustering of CD3ζ chains in a light-controlled manner. In the cited study, clustering was sufficient to drive proximal signaling outputs, and in reconstituted COS-7 cells Lck expression alone was required to initiate CD3ζ phosphorylation upon clustering.
Compared with CRY2-CIBN optogenetic system
light-controlled optogenetic CD3ζ clustering tool and CRY2-CIBN optogenetic system address a similar problem space because they share localization, signaling.
Shared frame: same top-level item type; shared target processes: localization, signaling; same primary input modality: light
Compared with fusion proteins with large N-terminal anchors
light-controlled optogenetic CD3ζ clustering tool and fusion proteins with large N-terminal anchors address a similar problem space because they share localization, signaling.
Shared frame: same top-level item type; shared target processes: localization, signaling; same primary input modality: light
Compared with LOVpep/ePDZb
light-controlled optogenetic CD3ζ clustering tool and LOVpep/ePDZb address a similar problem space because they share localization, signaling.
Shared frame: same top-level item type; shared target processes: localization, signaling; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.