Membrane Recruitment

BcLOV4 is a blue-light-responsive photoreceptor from Botrytis cinerea that functions as a single-component optogenetic module for rapid plasma membrane recruitment. Illumination drives cytosol-to-membrane translocation through direct protein-lipid electrostatic interaction, and fused cargo such as RhoA GTPase or RhoA-activating GEFs can be relocalized to the membrane with light.

The CRY2-talin/CIBN-CAAX optogenetic plasma membrane recruitment system is a blue-light-responsive two-component switch that fuses Arabidopsis cryptochrome 2 to the N terminus of full-length talin and anchors the N-terminal cryptochrome-interacting basic helix-loop-helix domain to the plasma membrane with a CAAX motif. In Chinese hamster ovary cells and endothelial cells, 450 nm illumination recruits talin to the plasma membrane and promotes activation of β3 integrins, including αIIbβ3- and αVβ3-associated complexes.

CRY2/CIB1 is a blue-light-inducible multi-component interaction switch composed of the photoreceptor CRY2 and its interacting partner CIB1. It is used for acute light-dependent protein recruitment, including plasma-membrane recruitment and clustering, to control protein localization and downstream signaling with high spatial and temporal resolution.

iLID/SspB is a blue-light-inducible heterodimerization system built from an engineered iLID module and the SspB binding partner. It is used to reversibly recruit proteins in cells for control of localization and signaling, including membrane recruitment, neurotrophin receptor construction, microtubule plus-end targeting, and perturbation of small GTPase pathways.

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.

Light-inducible TrkA activation strategies comprise four engineered optical designs for activating TrkA signaling without nerve growth factor. The reported approaches use light to drive plasma membrane recruitment and homo-interaction of the intracellular domain of TrkA, recapitulating native NGF/TrkA-associated functions.

The near-infrared non-opsin optogenetic tool for nuclear export is a genetically encoded multi-component system that induces nuclear export of a protein of interest in response to near-infrared light. In darkness, its effect is reversed by nuclear import, so subcellular localization depends on the balance between light-driven export and NLS-mediated import.

Opto-Akt is an optogenetic construct used to activate or target Akt with light in order to interrogate Akt-dependent signaling and subcellular localization. In adipocytes, its light-driven activity only partially triggered IRAP-pHluorin translocation, indicating that isolated Akt activation does not fully reproduce insulin-like trafficking responses.

This tool is a rapid and reversible optogenetic switch for the yeast Set2 methyltransferase generated by fusing Set2, the sole H3K36 methyltransferase in yeast, to the light-activated nuclear shuttle (LANS) domain. It uses light to control Set2 subcellular localization and was applied to interrogate in vivo H3K36me2 and H3K36me3 dynamics.

p21-CRY2/CIB1 is a blue-light-responsive optogenetic p21 system built by fusing p21 to the cryptochrome 2/CIBN switch components. It was used to control p21 subcellular localization and nuclear function and increased the fraction of cells arrested in G1 phase.

p21-LINuS is a light-controllable p21 construct created by fusing p21 to the AsLOV-based light-inducible nuclear localization signal (LINuS). It was used to optogenetically control p21 subcellular localization and nuclear function, increasing the fraction of cells arrested in G1 phase under blue LED illumination.

The re-engineered MLKL membrane recruitment tool is a single-component optogenetic system derived from MLKL that preserves light-mediated plasma membrane recruitment while blocking MLKL-associated cell-killing activity. It is intended to modulate protein function through light-controlled localization at the plasma membrane.

The Rho1-CRY2 fusion construct is a proposed optogenetic multi-component switch for Drosophila in which a small G protein Rho variant would be fused to CRY2. The intended function is blue-light-dependent recruitment of Rho1-CRY2 to membrane-anchored CIB to control subcellular localization and downstream events, but the available evidence indicates the construct was still being cloned rather than functionally validated.

The light-activated nuclear shuttle (LANS) domain is a protein domain used as a fusion module to confer light-controlled subcellular localization. In the cited 2020 yeast study, fusion of LANS to the Set2 methyltransferase enabled rapid and reversible optogenetic control of Set2 function.

LINuS is a small genetically encoded protein domain for optogenetic control of subcellular localization. When fused to a protein of interest at either the N terminus or C terminus, it reversibly drives nuclear import in response to blue light.

Light-inducible nuclear localization signals are engineered protein-domain tools that enable light-dependent control of nuclear import in living cells. The available evidence supports their use for precise spatiotemporal regulation of protein dynamics through control of subcellular localization.