DS0501 - Biologie des animaux, des végétaux, des micro-organismes et adaptation aux changements environnementaux

Nuclear Activities of DNA-Associated Immune Receptors – RADAR

Submission summary

In plant and animal innate immunity, individual cells express receptor proteins to discriminate between pathogenic and non-pathogenic organisms. Pattern recognition receptors (PRRs) bind conserved pathogen molecules (pathogen-associated molecular patterns, PAMPs) to trigger a first line of resistance known as pattern-triggered immunity (PTI). Further pathogen interference is monitored inside cells by families of intracellular nucleotide-binding/leucine-rich-repeat receptors (NLRs). Plant NLRs recognize variable pathogen-derived virulence factors (called effectors) that are delivered into host cells to dampen PTI basal resistance pathways. NLR immune receptors behave as molecular switches that undergo conformational changes from auto-inhibited to activated molecules in response to pathogen. Structurally defective or misregulated NLRs can lead to autoimmunity which disturbs growth and fitness emphasizing the importance of tight control over NLR activation and signaling. Although various NLR activation events are becoming more transparent, the mechanisms by which NLRs mobilize immunity pathways remain obscure.

This proposal aims to elucidate receptor signaling dynamics at the chromatin during transcriptional reprogramming in ETI controlled by a co-functioning Arabidopsis NLR pair, RRS1-R (RESISTANCE TO RALSTONIA SOLANACEARUM1) and RPS4 (RESISTANCE TO PSEUDOMONAS SYRINGAE4), that confers resistance to different pathogens, including root-infecting Ralstonia solanacearum bacteria expressing a type-III secreted effector (T3SE), PopP2, and leaf-infecting Pseudomonas syringae pv pisi bacteria secreting an unrelated T3SE, AvrRps4.

Molecular and structural analyses of RRS1-R/RPS4 interactions suggest that a heterodimer represents a pre-activation receptor complex which is activated by direct binding of PopP2 or AvrRps4 to RRS1-R. Recently, P1 (Deslandes) and P2 (Parker) elucidated the mechanism by which PopP2 triggers RRS1-R/RPS4 activation. PopP2 acetylation of a key lysine within the WRKY DNA-binding domain of RRS1-R disrupts RRS1-R DNA association and activates RPS4-dependent immunity. PopP2 employs this lysine acetylation strategy to target multiple defense-promoting WRKY transcription factors, causing loss of WRKY-DNA binding and transactivating functions needed for defense gene expression. Thus, RRS1-R represents a DNA-bound immune receptor with an integrated effector decoy, which directly converts an essential pathogen virulence activity into immunity (Cell, in press).

RRS1-R/RPS4 immunity depends on lipase-like ENHANCED DISEASE SENSITIVITY1 (EDS1), a nuclear basal and TNL immunity regulator that interacts with PHYTOALEXIN DEFICIENT4 (PAD4) or SENESCENCE ASSOCIATED GENE1 (SAG101). By resolving the crystal structure of EDS1 in a heterodimeric complex with SAG101, the P2 and P3 (Niefind) labs recently explained the requirement of EDS1-PAD4 or EDS1-SAG101 heteromeric complexes for Arabidopsis basal immunity and ETI. EDS1 that interacts with several TNLs, including RPS4, is a prime candidate protein for direct transmission of signals from effector-activated immune complexes at the chromatin to the transcriptional reprogramming of cells. We hypothesize that RRS1-R anchors an RRS1-R/RPS4/EDS1 complex at specific chromatin sites, thereby providing a chromatin context for EDS1-mediated transcriptional reprogramming in ETI. AvrRps4 and PopP2 activities might converge on a chromatin hub guarded by this immune receptor complex whose dislodging from DNA drives resistance pathway activation. Here, the P1, P2 and P3 partners bring together complementary skills and materials to pursue molecular genetic, genomic and protein structural/biophysical approaches for unravelling NLR dynamics at the DNA. This proposal will uncover some gaps in our understanding of how the active state of NLRs connects to downstream signaling events and how these are integrated for timely and balanced host transcriptional defense responses in ETI.

Project coordination

Laurent Deslandes (Centre National de la Recherche Scientifique/Laboratoire des Interactions Plantes Micro-organismes)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CNRS/LIPM Centre National de la Recherche Scientifique/Laboratoire des Interactions Plantes Micro-organismes
MPIPZ Max-Planck Institut
IBUC Institute of Biochemistry/University of Cologne

Help of the ANR 284,260 euros
Beginning and duration of the scientific project: November 2015 - 36 Months

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