Source 1primary paper2022Cell Death Discovery
Toolkit/light-activated MLKL
light-activated MLKL
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Light-activated MLKL is an engineered optogenetic MLKL system that undergoes rapid light-triggered oligomerization and plasma membrane recruitment, causing rapid cell death. A re-engineered variant blocks the cell-killing activity while retaining light-mediated membrane recruitment, enabling single-component control of protein function at the plasma membrane.
Usefulness & Problems
Why this is useful
This tool provides spatiotemporal optical control over MLKL-dependent plasma membrane recruitment and necroptotic effector activity in cells. The nonlethal re-engineered variant extends this utility to single-component manipulation of protein function at the plasma membrane without triggering cell death.
Problem solved
It addresses the need for precise, light-gated control of necroptotic cell death and membrane-localized protein perturbation in living cells. It was also applied to interrogate signaling responses in non-dying bystander cells during optically induced death signaling.
Problem links
Need better screening or enrichment leverage
DerivedLight-activated MLKL is an engineered optogenetic MLKL system that undergoes rapid light-triggered oligomerization and plasma membrane recruitment, leading to rapid cell death. A re-engineered variant also retains light-mediated membrane recruitment while blocking cell-killing activity, enabling single-component control of protein function at the plasma membrane.
Need conditional control of signaling activity
DerivedLight-activated MLKL is an engineered optogenetic MLKL system that undergoes rapid light-triggered oligomerization and plasma membrane recruitment, leading to rapid cell death. A re-engineered variant also retains light-mediated membrane recruitment while blocking cell-killing activity, enabling single-component control of protein function at the plasma membrane.
Need conditional recombination or state switching
DerivedLight-activated MLKL is an engineered optogenetic MLKL system that undergoes rapid light-triggered oligomerization and plasma membrane recruitment, leading to rapid cell death. A re-engineered variant also retains light-mediated membrane recruitment while blocking cell-killing activity, enabling single-component control of protein function at the plasma membrane.
Need precise spatiotemporal control with light input
DerivedLight-activated MLKL is an engineered optogenetic MLKL system that undergoes rapid light-triggered oligomerization and plasma membrane recruitment, leading to rapid cell death. A re-engineered variant also retains light-mediated membrane recruitment while blocking cell-killing activity, enabling single-component control of protein function at the plasma membrane.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
light-triggered oligomerizationOligomerizationOligomerizationplasma membrane recruitmentplasma membrane recruitmentTechniques
Functional AssayFunctional AssayFunctional AssaySelection / EnrichmentSelection / EnrichmentSelection / EnrichmentTarget processes
recombinationselectionsignalingInput: 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 available evidence indicates that the system is an engineered MLKL construct used in cells and activated by light to drive oligomerization and plasma membrane recruitment. The evidence provided does not report cofactors, expression system details, delivery modality, or specific fusion design.
The supplied evidence does not specify the photosensory domain, illumination wavelength, construct architecture, or quantitative performance metrics. Validation described here is limited to the source study, and independent replication is not provided in the evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death. Derived from claim c1. Quoted text: we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
Supporting Sources
Ranked Claims
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
MLKL was re-engineered to block cell-killing capacity while retaining light-mediated membrane recruitment, yielding a single-component optogenetic tool for modulation of protein function at the plasma membrane.
we re-engineered MLKL to block its cell-killing capacity but retain light-mediated membrane recruitment, developing a new single-component optogenetic tool that allows modulation of protein function at the plasma membrane
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
Approval Evidence
1 source4 linked approval claimsfirst-pass slug light-activated-mlkl
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
engineered functionsupports
A light-activated version of MLKL was engineered that rapidly oligomerizes, is recruited to the plasma membrane upon light exposure, and induces rapid cell death.
we engineered a light-activated version of MLKL that rapidly oligomerizes and is recruited to the plasma membrane in cells exposed to light, inducing rapid cell death
Source:
research applicationsupports
The light-activated MLKL tool was used to study signaling responses of non-dying bystander cells.
used to study signaling responses of non-dying bystander cells
Source:
screening applicationsupports
The light-activated MLKL tool was used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death.
used in a chemical genetic screen to identify chemicals and pathways that protect cells from MLKL-induced cell death
Source:
spatiotemporal controlsupports
The light-activated MLKL tool can be controlled spatially and temporally.
We demonstrate this tool can be controlled spatially and temporally
Source:
Comparisons
Source-backed strengths
The reported system rapidly oligomerizes and relocalizes to the plasma membrane upon light exposure, producing rapid cell death. A second engineered form preserves light-mediated membrane recruitment while eliminating killing activity, broadening the functional range of the platform.
Compared with CRY2/CIB1
light-activated MLKL and CRY2/CIB1 address a similar problem space because they share recombination, signaling.
Shared frame: same top-level item type; shared target processes: recombination, signaling; shared mechanisms: oligomerization; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with human Neuropsin
light-activated MLKL and human Neuropsin address a similar problem space because they share recombination, selection, signaling.
Shared frame: same top-level item type; shared target processes: recombination, selection, signaling; same primary input modality: light
Compared with light-switchable transcription factors
light-activated MLKL and light-switchable transcription factors address a similar problem space because they share recombination, selection.
Shared frame: same top-level item type; shared target processes: recombination, selection; same primary input modality: light
Ranked Citations
- 1.