A phase-separated nuclear GBPL circuit controls immunity in plants

Shuai Huang, Shiwei Zhu, Pradeep Kumar and John D. MacMicking ()
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Shuai Huang: Howard Hughes Medical Institute
Shiwei Zhu: Howard Hughes Medical Institute
Pradeep Kumar: Howard Hughes Medical Institute
John D. MacMicking: Howard Hughes Medical Institute

Nature, 2021, vol. 594, issue 7863, 424-429

Abstract: Abstract Liquid–liquid phase separation (LLPS) has emerged as a central paradigm for understanding how membraneless organelles compartmentalize diverse cellular activities in eukaryotes1–3. Here we identify a superfamily of plant guanylate-binding protein (GBP)-like GTPases (GBPLs) that assemble LLPS-driven condensates within the nucleus to protect against infection and autoimmunity. In Arabidopsis thaliana, two members of this family—GBPL1 and GBPL3—undergo phase-transition behaviour to control transcriptional responses as part of an allosteric switch that is triggered by exposure to biotic stress. GBPL1, a pseudo-GTPase, sequesters catalytically active GBPL3 under basal conditions but is displaced by GBPL3 LLPS when it enters the nucleus following immune cues to drive the formation of unique membraneless organelles termed GBPL defence-activated condensates (GDACs) that we visualized by in situ cryo-electron tomography. Within these mesoscale GDAC structures, native GBPL3 directly bound defence-gene promoters and recruited specific transcriptional coactivators of the Mediator complex and RNA polymerase II machinery to massively reprogram host gene expression for disease resistance. Together, our study identifies a GBPL circuit that reinforces the biological importance of phase-separated condensates, in this case, as indispensable players in plant defence.

Date: 2021
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DOI: 10.1038/s41586-021-03572-6

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