Optogenetic control of the Bone Morphogenetic Protein signalling pathway through engineered blue light-sensitive receptorsCitation formats

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@article{a7a2758280a24e549c6a19df614351ef,
title = "Optogenetic control of the Bone Morphogenetic Protein signalling pathway through engineered blue light-sensitive receptors",
abstract = "Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise perturbation of the BMP signalling pathway. Here, we develop a novel optogenetic BMP signalling system (optoBMP) that enables rapid induction of the canonical BMP signalling pathway through illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signalling pathway through variable light stimulation. Optogenetic control of BMP signalling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.",
keywords = "Optogenetics, Cell signalling, BMP signalling, Chondrocytes, LOV domain",
author = "Paul Humphreys and Steven Woods and Christopher Smith and Nicola Bates and Stuart Cain and Robert Lucas and Susan Kimber",
year = "2020",
month = oct,
day = "21",
doi = "10.1021/acssynbio.0c00315",
language = "English",
journal = "ACS Synthetic Biology",
issn = "2161-5063",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Optogenetic control of the Bone Morphogenetic Protein signalling pathway through engineered blue light-sensitive receptors

AU - Humphreys, Paul

AU - Woods, Steven

AU - Smith, Christopher

AU - Bates, Nicola

AU - Cain, Stuart

AU - Lucas, Robert

AU - Kimber, Susan

PY - 2020/10/21

Y1 - 2020/10/21

N2 - Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise perturbation of the BMP signalling pathway. Here, we develop a novel optogenetic BMP signalling system (optoBMP) that enables rapid induction of the canonical BMP signalling pathway through illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signalling pathway through variable light stimulation. Optogenetic control of BMP signalling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

AB - Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise perturbation of the BMP signalling pathway. Here, we develop a novel optogenetic BMP signalling system (optoBMP) that enables rapid induction of the canonical BMP signalling pathway through illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signalling pathway through variable light stimulation. Optogenetic control of BMP signalling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

KW - Optogenetics

KW - Cell signalling

KW - BMP signalling

KW - Chondrocytes

KW - LOV domain

U2 - 10.1021/acssynbio.0c00315

DO - 10.1021/acssynbio.0c00315

M3 - Article

JO - ACS Synthetic Biology

JF - ACS Synthetic Biology

SN - 2161-5063

ER -