A phase-separated nuclear GBPL circuit controls immunity in plants

Liquid-liquid phase separation (LLPS) has emerged as a central paradigm for understanding how membrane-less organelles compartmentalize diverse cellular activities in eukaryotes. Here, we identified a new superfamily of plant Guanylate-Binding Protein-Like GTPases (GBPLs) that assemble LLPS-driven condensates within the nucleus to protect against infection and autoimmunity. In Arabidopsis thaliana, two family members - GBPL1 and GBPL3 - undergo phase transition behavior to control transcriptional responses as part of an allosteric switch triggered by exposure to biotic stress. GBPL1, a pseudoGTPase, sequesters catalytically-active GBPL3 under basal conditions but is displaced by GBPL3 LLPS when it enters the nucleus following immune cues to drive formation of unique membrane-less organelles termed GDACs (GBPL Defense-Activated Condensates) that we visualized by in situ cryo-electron tomography. Within these mesoscale GDAC structures, native GBPL3 directly bound defense gene promoters and recruited specific transcriptional coactivators of the Mediator complex plus RNA Pol II machinery to massively reprogram host gene expression for disease resistance. Together, our study identifies a new GBPL circuit that reinforces the biological importance of phase-separated condensates, in this case, as indispensable players in plant defense.Funding provided by: Howard Hughes Medical InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000011Award Number